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1.
Planta ; 254(4): 67, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495419

RESUMO

MAIN CONCLUSION: Transcriptomic and volatile component analyses showed that high expression levels of genes from the terpenoid backbone biosynthesis pathway and the monoterpene metabolic pathway can strengthen the floral fragrance of tree peony. Floral fragrance is a crucial ornamental trait whose improvement is one of the primary objectives of tree peony breeding. So far, exploration of the floral fragrance of tree peony has focused on the identification of its volatile components, but the molecular mechanisms responsible for their formation remain unclear. Here, we identified 128 volatile components from the petals of tree peony and found that they consisted primarily of terpenes, alcohols, and esters. Based on the distribution pattern of these major fragrance components, 24 tree peony cultivars were classified into 4 types: grassy scent (ocimene), woody scent (longifolene), lily of the valley scent (linalool), and fruity scent (2-ethyl hexanol). We used RNA-seq to explore the mechanistic basis of terpenoid metabolism in tree peony petals with various scents. The expression levels of AACT, HMGR, PMK, DXS, DXR, HDS, HDR, and GGPS, which encode key enzymes of terpenoid backbone biosynthesis, were upregulated in 'Huangguan' (strong fragrance) compared to 'Fengdan' (faint fragrance). Moreover, the transcript abundance of LIS and MYS, two monoterpene synthase genes, was also enhanced in petals of 'Huangguan' compared to those of 'Fengdan'. Together, these results demonstrate that differences in the expression of genes from the monoterpene synthesis and terpenoid backbone pathways are associated with differences in the fragrance of tree peony. This research provides crucial genetic resources for fragrance improvement and also lays a foundation for further clarification of the mechanisms that underlie tree peony fragrance.


Assuntos
Paeonia , Flores/genética , Regulação da Expressão Gênica de Plantas , Paeonia/genética , Melhoramento Vegetal , Terpenos , Transcriptoma/genética , Árvores
2.
J Transl Med ; 19(1): 388, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507566

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age of 68 in clinical diagnosis. About 60% patients are over 60 years old. There are various treatment options for AML patients. But for elderly patients, the complete remission rates are disappointing due to genetic, molecular, and age-related factors. Development of next-generation sequencing technologies makes it possible to seek individual strategies for patients in different ages. This study analyzed transcriptome profiles in platelets of AML patients in different ages for the first time. METHODS: Platelet RNA sequencing in AML of ten elderly and seven young patients were performed with Illumina TruSeq Stranded mRNA library Prep Kit and Illumina HiSeq4000 sequencing instrument. With the FASTQ sequencing data obtained, statistical analyses between elderly with young AML patients were analyzed by R program. GO and KEGG enrichment analyses were performed via R package clusterProfiler. TOP 10 down-regulated/up-regulated genes in elderly patients compared to young patients were selected with the threshold of |L2FC| > 2 and padj ≤ 0.0001. The down-regulated gene ATF4 was chosen by GSEA analysis and ROC analysis with AUC > 0.95. RESULTS: We found 3059 genes with differential transcript levels (GDTLs) in AML patients of different age. Among them, 2048 genes are down-regulated and 651 genes are up-regulated in elderly patients. We found that gene transcript profiles in elderly patients is obviously different from those in young patients, including a collection of down-regulated genes related to proteins processing in endoplasmic reticulum and immunity. We further identified that genes of pathway in cancer and mitogen activated protein kinase (MAPK) pathway, involved in natural immunity and metabolism, are significantly down-regulated in elderly patients. Among all screened genes with decreased transcript levels, we believe that activating transcription factor 4 (ATF4) is a biomarker indicating different chemotherapy strategies for elderly patients. CONCLUSIONS: In summary, gene transcript profiles are different in platelets of elderly and young AML patients. And ATF4 can be a useful biomarker indicating different chemotherapy strategies for AML patients with different ages.


Assuntos
Leucemia Mieloide Aguda , Transcriptoma , Adulto , Idoso , Plaquetas , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma/genética
3.
Microbiome ; 9(1): 182, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479645

RESUMO

BACKGROUND: Deep-sea animals in hydrothermal vents often form endosymbioses with chemosynthetic bacteria. Endosymbionts serve essential biochemical and ecological functions, but the prokaryotic viruses (phages) that determine their fate are unknown. RESULTS: We conducted metagenomic analysis of a deep-sea vent snail. We assembled four genome bins for Caudovirales phages that had developed dual endosymbiosis with sulphur-oxidising bacteria (SOB) and methane-oxidising bacteria (MOB). Clustered regularly interspaced short palindromic repeat (CRISPR) spacer mapping, genome comparison, and transcriptomic profiling revealed that phages Bin1, Bin2, and Bin4 infected SOB and MOB. The observation of prophages in the snail endosymbionts and expression of the phage integrase gene suggested the presence of lysogenic infection, and the expression of phage structural protein and lysozyme genes indicated active lytic infection. Furthermore, SOB and MOB appear to employ adaptive CRISPR-Cas systems to target phage DNA. Additional expressed defence systems, such as innate restriction-modification systems and dormancy-inducing toxin-antitoxin systems, may co-function and form multiple lines for anti-viral defence. To counter host defence, phages Bin1, Bin2, and Bin3 appear to have evolved anti-restriction mechanisms and expressed methyltransferase genes that potentially counterbalance host restriction activity. In addition, the high-level expression of the auxiliary metabolic genes narGH, which encode nitrate reductase subunits, may promote ATP production, thereby benefiting phage DNA packaging for replication. CONCLUSIONS: This study provides new insights into phage-bacteria interplay in intracellular environments of a deep-sea vent snail. Video Abstract.


Assuntos
Bacteriófagos , Animais , Bactérias/genética , Bacteriófagos/genética , Genômica , Proteômica , Caramujos , Transcriptoma/genética
4.
Nat Commun ; 12(1): 4797, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376651

RESUMO

Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/-; Tcf12+/- mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.


Assuntos
Suturas Cranianas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Osteogênese/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Acrocefalossindactilia/embriologia , Acrocefalossindactilia/genética , Acrocefalossindactilia/patologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Suturas Cranianas/citologia , Suturas Cranianas/embriologia , Dura-Máter/citologia , Dura-Máter/embriologia , Dura-Máter/metabolismo , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Osteoblastos/citologia , Osteoblastos/metabolismo , RNA-Seq/métodos , Crânio/citologia , Crânio/embriologia , Crânio/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
5.
FASEB J ; 35(9): e21752, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34369602

RESUMO

Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1ß coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1ß [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1α4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.


Assuntos
Tecido Adiposo/metabolismo , Mitocôndrias/genética , Proteínas Nucleares/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Fatores de Transcrição/genética , Envelhecimento/genética , Animais , Modelos Animais de Doenças , Metabolismo Energético/genética , Heterozigoto , Resistência à Insulina/genética , Masculino , Camundongos , Obesidade/genética , Termogênese/genética , Transcriptoma/genética
6.
Biomolecules ; 11(7)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34356594

RESUMO

(1) Background: The interaction of the programmed death receptor (PD-1) with its ligand 1 (PD-L1) allows cancer cells to escape from the control of the immune system. Research evaluating the expression of immune checkpoint genes in the tissues of laryngeal tumors may contribute to the introduction of new effective immunotherapeutic methods in this group of neoplasms. The aim of this study was to evaluate the expression of the gene for the programmed death receptor (PD-1) and its ligand (PD-L1) in laryngeal tumors (T1, T2, T3) in patients without lymph node involvement and distant metastases. (2) Methods: The study included 73 patients: 39 of them were diagnosed with carcinoma planoepiteliale keratodes (study group) and 34 with nasal septal deviation undergoing septoplasty (control group). Biological material for molecular tests (Real time PCR) was collected during surgical procedures. Furthermore, all study participants completed a questionnaire regarding, among others, smoking and body weight. (3) Results: Gene expression for programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) was, statistically, significantly higher (p < 0.0001) in tumor tissue than in unchanged mucosa. Moreover, it was found that the greater the tumor size, the higher the expression level of the tested molecules. (4) Conclusions: Although further research on the role of the PD-1/PD-L1 pathway in laryngeal tumors is necessary, the presented reports are promising and may constitute a contribution to considerations on the introduction of targeted immunotherapy with anti-PD1 and anti-PD-L1 monoclonal antibodies in the treatment of these tumors.


Assuntos
Antígeno B7-H1/genética , Neoplasias Laríngeas/genética , Receptor de Morte Celular Programada 1/genética , Idoso , Anticorpos Monoclonais/genética , Antígeno B7-H1/metabolismo , Estudos de Coortes , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imunoterapia/métodos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/fisiopatologia , Ligantes , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Morte Celular/genética , Receptores de Morte Celular/metabolismo , Transcriptoma/genética
7.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360778

RESUMO

G-quadruplexes are the non-canonical nucleic acid structures that are preferentially formed in G-rich regions. This structure has been shown to be associated with many biological functions. Regardless of the broad efforts on DNA G-quadruplexes, we still have limited knowledge on RNA G-quadruplexes, especially in a transcriptome-wide manner. Herein, by integrating the DMS-seq and the bioinformatics pipeline, we profiled and depicted the RNA G-quadruplexes in the human transcriptome. The genes that contain RNA G-quadruplexes in their specific regions are significantly related to immune pathways and the COVID-19-related gene sets. Bioinformatics analysis reveals the potential regulatory functions of G-quadruplexes on miRNA targeting at the scale of the whole transcriptome. In addition, the G-quadruplexes are depleted in the putative, not the real, PAS-strong poly(A) sites, which may weaken the possibility of such sites being the real cleaved sites. In brief, our study provides insight into the potential function of RNA G-quadruplexes in post-transcription.


Assuntos
Quadruplex G , Transcriptoma/genética , COVID-19/genética , Linhagem Celular , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , MicroRNAs/química , MicroRNAs/metabolismo , Poli A/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Regiões não Traduzidas/genética
8.
Front Immunol ; 12: 700152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394094

RESUMO

Background: Mucosal-associated invariant T (MAIT) cells are considered to participate of the host immune response against acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, single-cell transcriptomic profiling of MAIT cells in patients with COVID-19 remains unexplored. Methods: We performed single-cell RNA sequencing analyses on peripheral MAIT cells from 13 patients with COVID-19 and 5 healthy donors. The transcriptional profiles of MAIT cells, together with assembled T-cell receptor sequences, were analyzed. Flow cytometry analysis was also performed to investigate the properties of MAIT cells. Results: We identified that differentially expressed genes (DEGs) of MAIT cells were involved in myeloid leukocyte activation and lymphocyte activation in patients with COVID-19. In addition, in MAIT cells from severe cases, more DEGs were enriched in adaptive cellular and humoral immune responses compared with those in moderate cases. Further analysis indicated that the increase of cell cytotoxicity (killing), chemotaxis, and apoptosis levels in MAIT cells were consistent with disease severity and displayed the highest levels in patients with severe disease. Interestingly, flow cytometry analysis showed that the frequencies of pyroptotic MAIT cells, but not the frequencies of apoptotic MAIT cells, were increased significantly in patients with COVID-19, suggesting pyroptosis is one of leading causes of MAIT cell deaths during SARS-CoV-2 infection. Importantly, there were more clonal expansions of MAIT cells in severe cases than in moderate cases. Conclusions: The results of the present study suggest that MAIT cells are likely to be involved in the host immune response against SARS-CoV-2 infection. Simultaneously, the transcriptomic data from MAIT cells provides a deeper understanding of the immune pathogenesis of the disease.


Assuntos
COVID-19/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , SARS-CoV-2/imunologia , Transcriptoma/genética , Sequência de Bases , COVID-19/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Humanos , Ativação Linfocitária/genética , Piroptose/fisiologia , Análise de Sequência de RNA , Índice de Gravidade de Doença , Éxons VDJ/genética
9.
Front Immunol ; 12: 716075, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394120

RESUMO

The existence of asymptomatic and re-detectable positive coronavirus disease 2019 (COVID-19) patients presents the disease control challenges of COVID-19. Most studies on immune responses in COVID-19 have focused on moderately or severely symptomatic patients; however, little is known about the immune response in asymptomatic and re-detectable positive (RP) patients. Here we performed a comprehensive analysis of the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from 48 COVID-19 patients which included 8 asymptomatic, 13 symptomatic, 15 recovered and 12 RP patients. The weighted gene co-expression network analysis (WGCNA) identified six co-expression modules, of which the turquoise module was positively correlated with the asymptomatic, symptomatic, and recovered COVID-19 patients. The red module positively correlated with symptomatic patients only and the blue and brown modules positively correlated with the RP patients. The analysis by single sample gene set enrichment analysis (ssGSEA) revealed a lower level of IFN response and complement activation in the asymptomatic patients compared with the symptomatic, indicating a weaker immune response of the PBMCs in the asymptomatic patients. In addition, gene set enrichment analysis (GSEA) analysis showed the enrichment of TNFα/NF-κB and influenza infection in the RP patients compared with the recovered patients, indicating a hyper-inflammatory immune response in the PBMC of RP patients. Thus our findings could extend our understanding of host immune response during the progression of COVID-19 disease and assist clinical management and the immunotherapy development for COVID-19.


Assuntos
Doenças Assintomáticas , COVID-19/imunologia , Portador Sadio/imunologia , Leucócitos Mononucleares/imunologia , SARS-CoV-2/imunologia , Transcriptoma/genética , Adulto , Portador Sadio/virologia , Ativação do Complemento/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/imunologia , Influenza Humana/complicações , Interferons/sangue , Interferons/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transcriptoma/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
10.
Medicine (Baltimore) ; 100(32): e25909, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397867

RESUMO

ABSTRACT: Colorectal cancer is currently the third most common cancer around the world. In this study, we chose a bioinformatics analysis method based on network analysis to dig out the pathological mechanism and key prognostic targets of rectal adenocarcinoma (READ).In this study, we downloaded the clinical information data and transcriptome data from the Cancer Genome Atlas database. Differentially expressed genes analysis was used to identify the differential expressed genes in READ. Community discovery algorithm analysis and Correlation analysis between gene modules and clinical data were performed to mine the key modules related to tumor proliferation, metastasis, and invasion. Genetic significance (GS) analysis and PageRank algorithm analysis were applied for find key genes in the key module. Finally, the importance of these genes was confirmed by survival analysis.Transcriptome datasets of 165 cancer tissue samples and 9 paracancerous tissue samples were selected. Gene coexpression networks were constructed, multilevel algorithm was used to divide the gene coexpression network into 11 modules. From GO enrichment analysis, module 11 significantly associated with clinical characteristic N, T, and event, mainly involved in 2 types of biological processes which were highly related to tumor metastasis, invasion, and tumor microenvironment regulation: cell development and differentiation; the development of vascular and nervous systems. Based on the results of survival analysis, 7 key genes were found negatively correlated to the survival rate of READ, such as MMP14, SDC2, LAMC1, ELN, ACTA2, ZNF532, and CYBRD1.Our study found that these key genes were predicted playing an important role in tumor invasion and metastasis, and being associated with the prognosis of READ. This may provide some new potential therapeutic targets and thoughts for the prognosis of READ.


Assuntos
Adenocarcinoma/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Retais/genética , Transcriptoma/genética , Adenocarcinoma/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Prognóstico , Neoplasias Retais/metabolismo
11.
EBioMedicine ; 70: 103525, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392148

RESUMO

BACKGROUND: While our battle with the COVID-19 pandemic continues, a multitude of Omics data have been generated from patient samples in various studies. Translation of these data into clinical interventions against COVID-19 remains to be accomplished. Exploring host response to COVID-19 in the upper respiratory tract can unveil prognostic markers and therapeutic targets. METHODS: We conducted a meta-analysis of published transcriptome and proteome profiles of respiratory samples of COVID-19 patients to shortlist high confidence upregulated host factors. Subsequently, mRNA overexpression of selected genes was validated in nasal swabs from a cohort of COVID-19 positive/negative, symptomatic/asymptomatic individuals. Guided by this analysis, we sought to check for potential drug targets. An FDA-approved drug, Auranofin, was tested against SARS-CoV-2 replication in cell culture and Syrian hamster challenge model. FINDINGS: The meta-analysis and validation in the COVID-19 cohort revealed S100 family genes (S100A6, S100A8, S100A9, and S100P) as prognostic markers of severe COVID-19. Furthermore, Thioredoxin (TXN) was found to be consistently upregulated. Auranofin, which targets Thioredoxin reductase, was found to mitigate SARS-CoV-2 replication in vitro. Furthermore, oral administration of Auranofin in Syrian hamsters in therapeutic as well as prophylactic regimen reduced viral replication, IL-6 production, and inflammation in the lungs. INTERPRETATION: Elevated mRNA level of S100s in the nasal swabs indicate severe COVID-19 disease, and FDA-approved drug Auranofin mitigated SARS-CoV-2 replication in preclinical hamster model. FUNDING: This study was supported by the DBT-IISc partnership program (DBT (IED/4/2020-MED/DBT)), the Infosys Young Investigator award (YI/2019/1106), DBT-BIRAC grant (BT/CS0007/CS/02/20) and the DBT-Wellcome Trust India Alliance Intermediate Fellowship (IA/I/18/1/503613) to ST lab.


Assuntos
COVID-19/genética , Nasofaringe/virologia , Proteoma/genética , Transcriptoma/genética , Adulto , Animais , Biomarcadores/metabolismo , COVID-19/patologia , COVID-19/virologia , Linhagem Celular , Chlorocebus aethiops , Estudos de Coortes , Feminino , Células HEK293 , Humanos , Inflamação/genética , Inflamação/virologia , Interleucina-6/genética , Masculino , Mesocricetus , Pessoa de Meia-Idade , Nasofaringe/patologia , Pandemias , Prognóstico , RNA Mensageiro/genética , SARS-CoV-2/patogenicidade , Regulação para Cima/genética , Células Vero , Replicação Viral/genética
12.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445114

RESUMO

The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.


Assuntos
Bactérias/genética , Bactérias/patogenicidade , Transcriptoma/genética , Anticódon/genética , Humanos , Nucleosídeos/genética , Biossíntese de Proteínas/genética , Processamento Pós-Transcricional do RNA/genética , RNA de Transferência/genética , Virulência/genética
13.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445782

RESUMO

Spodoptera exigua is a worldwide pest afflicting edible vegetables and has developed varying levels of resistance to insecticides. Methoxyfenozide (MET), an ecdysteroid agonist, is effective against lepidopteran pests such as S. exigua. However, the mechanism of MET to S. exigua remains unclear. In this study, we analyzed the expression patterns of genes related to the ecdysone signaling pathway in transcriptome data treated with sublethal doses of MET and analyzed how expression levels of key genes affect the toxicity of MET on S. exigua. Our results demonstrated that 2639 genes were up-regulated and 2512 genes were down-regulated in S. exigua treated with LC30 of MET. Of these, 15 genes were involved in the ecdysone signaling pathway. qPCR results demonstrated that ecdysone receptor A (EcRA) expression levels significantly increased in S. exigua when treated with different doses of MET, and that the RNAi-mediated silencing of EcRA significantly increased mortality to 55.43% at 72 h when L3 S. exigua larvae were exposed to MET at the LC30 dose. Additionally, knocking down EcRA suppressed the most genes expressed in the ecdysone signaling pathway. The combination of MET and dsEcRA affected the expression of E74 and enhanced the expression of TREA. These results demonstrate that the adverse effects of sublethal MET disturb the ecdysone signaling pathway in S. exigua, and EcRA is closely related to MET toxic effect. This study increases our collective understanding of the mechanisms of MET in insect pests.


Assuntos
Ecdisona/genética , Hidrazinas/farmacologia , Hormônios Juvenis/farmacologia , Interferência de RNA/fisiologia , Transdução de Sinais/efeitos dos fármacos , Spodoptera/efeitos dos fármacos , Transcriptoma/genética , Animais , Perfilação da Expressão Gênica/métodos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Larva/genética , Receptores de Esteroides/genética , Spodoptera/genética
14.
J Transl Med ; 19(1): 368, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446056

RESUMO

BACKGROUND: Accumulative evidence shows that an organoid is a more practical and reliable tool in cancer biology research. This study aimed to identify and validate crucial genes involved in non-small cell lung cancer carcinogenesis and development using the transcriptomic analysis of tumor tissues and organoids. METHODS: Gene set enrichment analysis (GSEA) of tumor tissues, tumor organoids, and normal tissues was performed to reveal the similar and different mechanisms involved in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) carcinogenesis and progression. Differentially expressed gene analysis, prognostic analysis, and gene co-expression network analysis were further used to identify hub genes involved in LUAD and LUSC carcinogenesis and development. Finally, LUAD cell lines and organoids were used to validate these findings. RESULTS: GSEA analysis was performed to reveal the similar mechanisms involved in LUAD and LUSC carcinogenesis and development, such as P53 signaling pathway, base mismatch repair, DNA replication, cAMP signaling pathway and PPAR pathway. However, comparing with LUSC organoids, LUAD organoids showed downregulation of immune-related pathways, inflammation-related pathways, MAPK signaling pathways, and Rap1 signaling pathways, although these pathways were downregulated in LUAD and LUSC tissues by comparing with normal lung tissues. Further gene co-expression network analysis and prognostic analysis indicated CDK1, CCNB2, and CDC25A as the hub tumor-promoting genes in LUAD but not in LUSC, which were further validated in other datasets. Using LUAD cell lines and organoid models, CDK1 and CCNB2 knockdown were found to suppress LUAD proliferation. However, CDC25A knockdown did not inhibit LUAD cell line proliferation but could effectively suppress LUAD organoid growth, indicating that an organoid could be used as an effective tool to study cancer biology in LUAD. CONCLUSIONS: The results revealed CDK1, CCNB2, and CDC25A as the hub genes involved in LUAD carcinogenesis and development, which could be used as the potential biomarkers and targets for LUAD.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Organoides , Transcriptoma/genética
15.
Gene ; 805: 145908, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411649

RESUMO

Transcriptome profiling of Vrindavani and Tharparkar cattle (n = 5 each) revealed that more numbers of genes were dysregulated in Vrindavani than in Tharparkar. A contrast in gene expression was observed with 18.9 % of upregulated genes in Vrindavani downregulated in Tharparkar and 17.8% upregulated genes in Tharparkar downregulated in Vrindavani. Functional annotation of genes differentially expressed in Tharparkar and Vrindavani revealed that the systems biology in Tharparkar is moving towards counteracting the effects due to heat stress. Unlike Vrindavani, Tharparkar is not only endowed with higher expression of the scavengers (UBE2G1, UBE2S, and UBE2H) of misfolded proteins but also with protectors (VCP, Serp1, and CALR) of naïve unfolded proteins. Further, higher expression of the antioxidants in Tharparkar enables it to cope up with higher levels of free radicals generated as a result of heat stress. In this study, we found relevant genes dysregulated in Tharparkar in the direction that can counter heat stress.


Assuntos
Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/fisiologia , Animais , Bovinos/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Índia , Biologia de Sistemas/métodos , Transcriptoma/genética
16.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445148

RESUMO

The gram-positive pathogenic bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) causes bacterial canker disease in tomato, affecting crop yield and fruit quality. To understand how tomato plants respond, the dynamic expression profile of host genes was analyzed upon Cmm infection. Symptoms of bacterial canker became evident from the third day. As the disease progressed, the bacterial population increased in planta, reaching the highest level at six days and remained constant till the twelfth day post inoculation. These two time points were selected for transcriptomics. A progressive down-regulation of key genes encoding for components of the photosynthetic apparatus was observed. Two temporally separated defense responses were observed, which were to an extent interdependent. During the primary response, genes of the phenylpropanoid pathway were diverted towards the synthesis of monolignols away from S-lignin. In dicots, lignin polymers mainly consist of G- and S-units, playing an important role in defense. The twist towards G-lignin enrichment is consistent with previous findings, highlighting a response to generate an early protective barrier and to achieve a tight interplay between lignin recomposition and the primary defense response mechanism. Upon progression of Cmm infection, the temporal deactivation of phenylpropanoids coincided with the upregulation of genes that belong in a secondary response mechanism, supporting an elegant reprogramming of the host transcriptome to establish a robust defense apparatus and suppress pathogen invasion. This high-throughput analysis reveals a dynamic reorganization of plant defense mechanisms upon bacterial infection to implement an array of barriers preventing pathogen invasion and spread.


Assuntos
Regulação para Baixo/genética , Lycopersicon esculentum/genética , Lycopersicon esculentum/microbiologia , Fotossíntese/genética , Imunidade Vegetal/genética , Imunidade Vegetal/imunologia , Clavibacter/genética , Infecções por Bactérias Gram-Positivas/genética , Infecções por Bactérias Gram-Positivas/imunologia , Infecções por Bactérias Gram-Positivas/microbiologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Fotossíntese/imunologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Transcriptoma/genética , Regulação para Cima/genética
17.
BMC Res Notes ; 14(1): 306, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372933

RESUMO

OBJECTIVES: Complex algae are photosynthetic organisms resulting from eukaryote-to-eukaryote endosymbiotic-like interactions. Yet the specific lineages and mechanisms are still under debate. That is why large scale phylogenomic studies are needed. Whereas available proteomes provide a limited diversity of complex algae, MMETSP (Marine Microbial Eukaryote Transcriptome Sequencing Project) transcriptomes represent a valuable resource for phylogenomic analyses, owing to their broad and rich taxonomic sampling, especially of photosynthetic species. Unfortunately, this sampling is unbalanced and sometimes highly redundant. Moreover, we observed contaminated sequences in some samples. In such a context, tree inference and readability are impaired. Consequently, the aim of the data processing reported here is to release a unique set of clean and non-redundant transcriptomes produced through an original protocol featuring decontamination, pooling and dereplication steps. DATA DESCRIPTION: We submitted 678 MMETSP re-assembly samples to our parallel consolidation pipeline. Hence, we combined 423 samples into 110 consolidated transcriptomes, after the systematic removal of the most contaminated samples (186). This approach resulted in a total of 224 high-quality transcriptomes, easy to use and suitable to compute less contaminated, less redundant and more balanced phylogenies.


Assuntos
Eucariotos , Transcriptoma , Descontaminação , Eucariotos/genética , Filogenia , Plantas , Transcriptoma/genética
18.
FASEB J ; 35(9): e21830, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34342902

RESUMO

Muscle disuse leads to a rapid decline in muscle mass, with reduced muscle protein synthesis (MPS) considered the primary physiological mechanism. Here, we employed a systems biology approach to uncover molecular networks and key molecular candidates that quantitatively link to the degree of muscle atrophy and/or extent of decline in MPS during short-term disuse in humans. After consuming a bolus dose of deuterium oxide (D2 O; 3 mL.kg-1 ), eight healthy males (22 ± 2 years) underwent 4 days of unilateral lower-limb immobilization. Bilateral muscle biopsies were obtained post-intervention for RNA sequencing and D2 O-derived measurement of MPS, with thigh lean mass quantified using dual-energy X-ray absorptiometry. Application of weighted gene co-expression network analysis identified 15 distinct gene clusters ("modules") with an expression profile regulated by disuse and/or quantitatively connected to disuse-induced muscle mass or MPS changes. Module scans for candidate targets established an experimentally tractable set of candidate regulatory molecules (242 hub genes, 31 transcriptional regulators) associated with disuse-induced maladaptation, many themselves potently tied to disuse-induced reductions in muscle mass and/or MPS and, therefore, strong physiologically relevant candidates. Notably, we implicate a putative role for muscle protein breakdown-related molecular networks in impairing MPS during short-term disuse, and further establish DEPTOR (a potent mTOR inhibitor) as a critical mechanistic candidate of disuse driven MPS suppression in humans. Overall, these findings offer a strong benchmark for accelerating mechanistic understanding of short-term muscle disuse atrophy that may help expedite development of therapeutic interventions.


Assuntos
Proteínas Musculares/genética , Músculo Esquelético/fisiologia , Atrofia Muscular/genética , Doenças Musculares/genética , Biossíntese de Proteínas/genética , Transcriptoma/genética , Adulto , Humanos , Masculino , Força Muscular/genética , Adulto Jovem
19.
Nat Commun ; 12(1): 4821, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376672

RESUMO

Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.


Assuntos
Genoma Viral/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T do Adulto/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Adulto , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Cultivadas , Evolução Clonal/genética , Células Clonais/metabolismo , Células Clonais/patologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Células Jurkat , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Mutação , RNA-Seq/métodos , Receptor Notch1/genética , Receptores de Antígenos de Linfócitos T/genética , Fator de Transcrição STAT3/genética
20.
Nat Commun ; 12(1): 4907, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389726

RESUMO

The intestinal mucosa constitutes an environment of closely regulated immune cells. Dendritic cells (DC) interact with the gut microbiome and antigens and are important in maintaining gut homeostasis. Here, we investigate DC transcriptome, phenotype and function in five anatomical locations of the gut lamina propria (LP) which constitute different antigenic environments. We show that DC from distinct gut LP compartments induce distinct T cell differentiation and cytokine secretion. We also find that PD-L1+ DC in the duodenal LP and XCR1+ DC in the colonic LP comprise distinct tolerogenic DC subsets that are crucial for gut homeostasis. Mice lacking PD-L1+ and XCR1+ DC have a proinflammatory gut milieu associated with an increase in Th1/Th17 cells and a decrease in Treg cells and have exacerbated disease in the models of 5-FU-induced mucositis and DSS-induced colitis. Our findings identify PD-L1+ and XCR1+ DC as region-specific physiologic regulators of intestinal homeostasis.


Assuntos
Antígeno B7-H1/imunologia , Células Dendríticas/imunologia , Homeostase/imunologia , Mucosa Intestinal/imunologia , Receptores de Quimiocinas/imunologia , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Colite/genética , Colite/imunologia , Colite/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Homeostase/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transcriptoma/genética , Transcriptoma/imunologia
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