Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
3.
J Mol Biol ; : 167292, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624295

RESUMO

Liquid-liquid phase separation (LLPS) is an important mechanism that mediates the formation of biomolecular condensates. Despite the immense interest in LLPS, phase-separated proteins verified by experiments are still limited, and identification of phase-separated proteins at proteome-scale is a challenging task. Multivalent interaction among macromolecules is the driving force of LLPS, which suggests that phase-separated proteins may harbor distinct biological characteristics in protein-protein interactions (PPIs). In this study, we constructed an integrated human PPI network (HPIN) and mapped phase-separated proteins into it. Analysis of the network parameters revealed differences of network topology between phase-separated proteins and others. The results further suggested the efficiency when applying topological similarities in distinguishing components of MLOs. Furthermore, we found that affinity purification mass spectrometry (AP-MS) detects PPIs more effectively than yeast-two hybrid system (Y2H) in phase separation-driven condensates. Our work provides the first global view of the distinct network topology of phase-separated proteins in human interactome, suggesting incorporation of PPI network for LLPS prediction in further studies.

4.
Blood ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582557

RESUMO

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, undergoes large-cell transformation (LCT) in the late stage, manifesting aggressive behavior, resistance to treatments, and poor prognosis, but the mechanisms involved remain unclear. To identify the molecular driver of LCT, we collected tumor samples from 133 MF patients and performed whole-transcriptome sequencing on 49 advanced-stage MF patients, followed by integrated copy number inference and genomic hybridization. Tumors with LCT showed unique transcriptional programs and enriched expressions of genes at chr7q. Paternally expressed gene 10 (PEG10), an imprinted gene at 7q21.3, was ectopically expressed in malignant T cells from LCT, driven by 7q21.3 amplification. Mechanistically, aberrant PEG10 expression increased cell size, promoted cell proliferation, and conferred treatment resistance by a PEG10/KLF2/NF-κB axis in in vitro and in vivo models. Pharmacologically targeting PEG10 reversed the phenotypes of proliferation and treatment resistance in LCT. Our findings reveal new molecular mechanisms underlying LCT and suggest that PEG10 inhibition may serve as a promising therapeutic approach in late-stage aggressive T-cell lymphoma.

6.
Immunity ; 54(6): 1304-1319.e9, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34048708

RESUMO

Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.


Assuntos
COVID-19/metabolismo , COVID-19/virologia , Interações Hospedeiro-Patógeno , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Células Mieloides/imunologia , Células Mieloides/metabolismo , Proteínas de Neoplasias/metabolismo , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação , COVID-19/genética , Linhagem Celular , Citocinas , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Lectinas Tipo C/química , Proteínas de Membrana/química , Modelos Moleculares , Proteínas de Neoplasias/química , Ligação Proteica , Conformação Proteica , Anticorpos de Domínio Único/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-Atividade
7.
Genomics Proteomics Bioinformatics ; 19(2): 253-266, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662621

RESUMO

Single-cell RNA sequencing (scRNA-seq) is generally used for profiling transcriptome of individual cells. The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently used scRNA-seq platforms, yet there are only a few thorough and systematic comparisons of their advantages and limitations. Here, by directly comparing the scRNA-seq data generated by these two platforms from the same samples of CD45- cells, we systematically evaluated their features using a wide spectrum of analyses. Smart-seq2 detected more genes in a cell, especially low abundance transcripts as well as alternatively spliced transcripts, but captured higher proportion of mitochondrial genes. The composite of Smart-seq2 data also resembled bulk RNA-seq data more. For 10X-based data, we observed higher noise for mRNAs with low expression levels. Approximately 10%-30% of all detected transcripts by both platforms were from non-coding genes, with long non-coding RNAs (lncRNAs) accounting for a higher proportion in 10X. 10X-based data displayed more severe dropout problem, especially for genes with lower expression levels. However, 10X-data can detect rare cell types given its ability to cover a large number of cells. In addition, each platform detected distinct groups of differentially expressed genes between cell clusters, indicating the different characteristics of these technologies. Our study promotes better understanding of these two platforms and offers the basis for an informed choice of these widely used technologies.

8.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
10.
Cell ; 184(3): 792-809.e23, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33545035

RESUMO

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.


Assuntos
Células Mieloides/patologia , Neoplasias/genética , Neoplasias/patologia , Análise de Célula Única , Transcrição Genética , Linhagem Celular Tumoral , Linhagem da Célula , Células Dendríticas/metabolismo , Feminino , Humanos , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Macrófagos/metabolismo , Masculino , Mastócitos/patologia , Monócitos/metabolismo , Proteínas de Neoplasias/metabolismo , Transcriptoma/genética
11.
Annu Rev Immunol ; 39: 583-609, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637019

RESUMO

Understanding tumor immune microenvironments is critical for identifying immune modifiers of cancer progression and developing cancer immunotherapies. Recent applications of single-cell RNA sequencing (scRNA-seq) in dissecting tumor microenvironments have brought important insights into the biology of tumor-infiltrating immune cells, including their heterogeneity, dynamics, and potential roles in both disease progression and response to immune checkpoint inhibitors and other immunotherapies. This review focuses on the advances in knowledge of tumor immune microenvironments acquired from scRNA-seq studies across multiple types of human tumors, with a particular emphasis on the study of phenotypic plasticity and lineage dynamics of immune cells in the tumor environment. We also discuss several imminent questions emerging from scRNA-seq observations and their potential solutions on the horizon.


Assuntos
Neoplasias , Análise de Célula Única , Animais , Humanos , Imunoterapia , Neoplasias/terapia , Análise de Sequência de RNA , Microambiente Tumoral
12.
J Genet Genomics ; 47(7): 373-388, 2020 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-32998846

RESUMO

Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T-cell differentiation and activation, here, we proposed a computational method named IDEA (Isoform Detection, Enrichment, and functional Annotation) to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq data set of 12,346 T cells from non-small-cell lung cancer (NSCLC). We found that most genes tend to dominantly express one isoform in single T cells, enabling typing T cells based on the isotypes, given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/noncoding switches, transcription start site changes, gains/losses of domains, and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T-cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new light on the regulatory mechanisms of tumor-infiltrating T cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Isoformas de Proteínas/genética , Análise de Célula Única , Linfócitos T/metabolismo , Processamento Alternativo/genética , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Éxons/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Isoformas de Proteínas/imunologia , Análise de Sequência de RNA , Linfócitos T/imunologia , Linfócitos T/patologia
13.
Cell Res ; 30(9): 763-778, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32541867

RESUMO

Single-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Here we hypothesize that cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, and we present CSOmap, a computational tool to infer cellular interaction de novo from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of multiple organs of human and mouse including tumor microenvironments for multiple cancers in pseudo-space, and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be a widely applicable tool to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.


Assuntos
Receptores de Superfície Celular/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Transferência Adotiva , Comunicação Celular , Morte Celular , Bases de Dados Genéticas , Humanos , Imunidade , Ligantes , Neoplasias/patologia , Pâncreas/patologia , Fenótipo , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/patologia , Reprodutibilidade dos Testes , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Tetraspanina 30/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo
14.
Nat Commun ; 11(1): 3155, 2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572028

RESUMO

Single-cell RNA sequencing (scRNA-seq) is a versatile tool for discovering and annotating cell types and states, but the determination and annotation of cell subtypes is often subjective and arbitrary. Often, it is not even clear whether a given cluster is uniform. Here we present an entropy-based statistic, ROGUE, to accurately quantify the purity of identified cell clusters. We demonstrate that our ROGUE metric is broadly applicable, and enables accurate, sensitive and robust assessment of cluster purity on a wide range of simulated and real datasets. Applying this metric to fibroblast, B cell and brain data, we identify additional subtypes and demonstrate the application of ROGUE-guided analyses to detect precise signals in specific subpopulations. ROGUE can be applied to all tested scRNA-seq datasets, and has important implications for evaluating the quality of putative clusters, discovering pure cell subtypes and constructing comprehensive, detailed and standardized single cell atlas.


Assuntos
Análise de Dados , Análise de Sequência de RNA , Análise de Célula Única , Humanos , Modelos Teóricos , Análise de Sequência de RNA/métodos , Análise de Sequência de RNA/estatística & dados numéricos , Análise de Célula Única/métodos , Análise de Célula Única/estatística & dados numéricos , Software
15.
Sci China Life Sci ; 63(10): 1522-1533, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32303963

RESUMO

An improved understanding of the lung microbiome may lead to better strategies to diagnose, treat, and prevent pulmonary tuberculosis (PTB). However, the characteristics of the lung microbiomes of patients with TB remain largely undefined. In this study, 163 bronchoalveolar lavage (BAL) samples were collected from 163 sputum-negative suspected PTB patients. Furthermore, 12 paired BAL samples were obtained from 12 Mycobacterium tuberculosis-positive (MTB+) patients before and after negative conversion following a two-month anti-TB treatment. The V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to characterize the microbial composition of the lungs. The results showed that the prevalence of MTB in the BAL samples was 42.9% (70/163) among the sputum-negative patients. The α-diversity of lung microbiota was significantly less diverse in MTB+ patients compared with Mycobacterium tuberculosis-negative (MTB-) patients. There was a significant difference in ß-diversity between MTB+ and MTB- patients. MTB+ patients were enriched with Anoxybacillus, while MTB- patients were enriched with Prevotella, Alloprevotella, Veillonella, and Gemella. There was no significant difference between the Anoxybacillus detection rates of MTB+ and MTB- patients. The paired comparison between the BAL samples from MTB+ patients and their negative conversion showed that BAL negative-conversion microbiota had a higher α-diversity. In conclusion, distinct features of airway microbiota could be identified between samples from patients with and without MTB. Our results imply links between lung microbiota and different clinical groups of active PTB.


Assuntos
Pulmão/microbiologia , Microbiota , Tuberculose Pulmonar/microbiologia , Adulto , Antituberculosos/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Feminino , Humanos , Masculino , Microbiota/efeitos dos fármacos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , RNA Ribossômico 16S/genética , Tuberculose Pulmonar/tratamento farmacológico
16.
Cell ; 181(2): 442-459.e29, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32302573

RESUMO

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40+ Th1-like cells and CD8+ memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.


Assuntos
Neoplasias do Colo/patologia , Células Mieloides/metabolismo , Análise de Célula Única/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases/genética , Linfócitos T CD8-Positivos/imunologia , China , Neoplasias do Colo/terapia , Neoplasias Colorretais/patologia , Células Dendríticas/imunologia , Feminino , Humanos , Imunoterapia , Macrófagos/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Análise de Sequência de RNA/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
17.
Nat Commun ; 11(1): 1818, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286268

RESUMO

Fast, robust and technology-independent computational methods are needed for supervised cell type annotation of single-cell RNA sequencing data. We present SciBet, a supervised cell type identifier that accurately predicts cell identity for newly sequenced cells with order-of-magnitude speed advantage. We enable web client deployment of SciBet for rapid local computation without uploading local data to the server. Facing the exponential growth in the size of single cell RNA datasets, this user-friendly and cross-platform tool can be widely useful for single cell type identification.


Assuntos
Algoritmos , Análise de Célula Única , Bases de Dados como Assunto , Regulação da Expressão Gênica , Humanos , Internet , Reprodutibilidade dos Testes
18.
Bioinformatics ; 36(8): 2474-2485, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31845960

RESUMO

MOTIVATION: Single cell RNA-seq data offers us new resource and resolution to study cell type identity and its conversion. However, data analyses are challenging in dealing with noise, sparsity and poor annotation at single cell resolution. Detecting cell-type-indicative markers is promising to help denoising, clustering and cell type annotation. RESULTS: We developed a new method, scTIM, to reveal cell-type-indicative markers. scTIM is based on a multi-objective optimization framework to simultaneously maximize gene specificity by considering gene-cell relationship, maximize gene's ability to reconstruct cell-cell relationship and minimize gene redundancy by considering gene-gene relationship. Furthermore, consensus optimization is introduced for robust solution. Experimental results on three diverse single cell RNA-seq datasets show scTIM's advantages in identifying cell types (clustering), annotating cell types and reconstructing cell development trajectory. Applying scTIM to the large-scale mouse cell atlas data identifies critical markers for 15 tissues as 'mouse cell marker atlas', which allows us to investigate identities of different tissues and subtle cell types within a tissue. scTIM will serve as a useful method for single cell RNA-seq data mining. AVAILABILITY AND IMPLEMENTATION: scTIM is freely available at https://github.com/Frank-Orwell/scTIM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
RNA-Seq , Análise de Célula Única , Algoritmos , Animais , Consenso , Camundongos , Análise de Sequência de RNA , Software
19.
Cell ; 179(4): 829-845.e20, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675496

RESUMO

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.


Assuntos
Carcinoma Hepatocelular/imunologia , Proteínas de Transporte de Cátions/genética , Inflamação/imunologia , Neoplasias Hepáticas/imunologia , Glicoproteínas de Membrana/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Antígenos Comuns de Leucócito/imunologia , Fígado/imunologia , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Linfócitos/patologia , Glicoproteínas de Membrana Associadas ao Lisossomo/genética , Macrófagos/imunologia , Macrófagos/patologia , Células Mieloides/imunologia , Células Mieloides/patologia , Proteínas de Neoplasias/genética , Análise de Sequência de RNA , Análise de Célula Única , Transcriptoma/genética , Transcriptoma/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
20.
Adv Immunol ; 144: 217-245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31699218

RESUMO

The clinical success of immune checkpoint blockade provides great hope for curing cancers. However, the patient responses are not even. Precise understanding of tumor immunity is necessary to improving the current cancer immunotherapies and to developing new treatment options. Here we applied full-length single cell RNA-seq (scRNA-seq) to three cancer types and provide a comprehensive single T cell data resource for understanding various characteristics of tumor-infiltrating T cells. We also developed an analytical framework named as STARTRAC to quantitatively characterize the dynamic properties of various T cell subsets including tissue preference, clonal expansion, migration, and state transitions from the scRNA-seq snapshots of tumor immune microenvironments. Conserved and cancer type-specific T cell subsets and developmental patterns were revealed, and detailed molecular portrait of the tumor immunity-relevant T cell clusters were provided, shedding lights into the cellular and molecular mechanisms underlying the composition, heterogeneity, and formation of tumor immune microenvironments. Important genes such as LAYN and IGFLR1 also provided new options for future development of cancer therapeutics.


Assuntos
Carcinoma Hepatocelular/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Neoplasias Colorretais/imunologia , Neoplasias Hepáticas/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Colorretais/genética , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , RNA-Seq , Análise de Célula Única , Subpopulações de Linfócitos T/imunologia , Microambiente Tumoral/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...