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1.
J Am Chem Soc ; 142(45): 19346-19353, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33140964

RESUMO

A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.

2.
Int J Clin Exp Pathol ; 13(10): 2608-2611, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33165427

RESUMO

OBJECTIVE: To report an unusual case describing a plexiform Schwannoma in the ear cavity of a young child. PATIENT: A 3-year-old girl. INTERVENTIONS: The tumor was entirely removed by surgery, the pathologic diagnosis of the isolated tissue was performed, and the surgical incision was routinely treated. MAIN OUTCOME MEASURE: Report the main clinical manifestations and rehabilitation status of patients before, during and after surgery. RESULTS: By surgery, we completely removed the mass. Unlike previous literature reports, we found that the surface of the mass was not encapsulated, and subsequent pathologic reports confirmed that it was indeed a plexiform schwannoma. As of now, the patient did not have adverse reactions or postoperative recurrence. CONCLUSIONS: We recommend a pathologic diagnosis of isolated tissues after they are completely removed during surgery. Furthermore, if the same ear has been operated on before, it may increase the difficulty of this operation.

3.
Food Chem ; : 128521, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33162254

RESUMO

Magnetic graphene oxide/TiO2(MGO/TiO2) nanocomposite was synthesized for the reduction of aflatoxin B1 (AFB1) in corn oil. The photodegradation of synthesized nanocomposites on AFB1 in corn oil under different treatment conditions and its effect on the quality of corn oil were investigated. The doping of magnetic GO effectively enhanced the photocatalytic activity of TiO2 both under UV light and visible light. The reduction of AFB1 in corn oil reached 96.4% after illumination for 120 min under UV-Vis light. Holes (h+) and the hydroxyl radicals (OH) were found to play important roles in the reduction of AFB1, and three transformation products were confirmed by electrospray ionization mass spectrometry (ESI/MS) analysis. In addition, the quality of the treated corn oil was still acceptable after storage for 180 days. This study provides an effective, environmental-friendly and practical approach for reduction of AFB1 in oil products.

4.
Exp Gerontol ; 141: 111098, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33010330

RESUMO

Studying the changes of serum N-glycome during mouse aging is beneficial to explore the molecular basis behind the alterations reported in human. However, such studies remainscarce and lack some information such as sialylation due to the method limitation. Here, we introduced Bionic Glycome method to quantify the serum N-glycome changes during C57BL/6 mouse aging (from the pubertal period to the old age stage). This technique enabled reliable and comprehensive quantitation of the expression level changes of more than 20 N-glycans in mouse serum at 12 time points in both genders for the first time, involving the analysis of sialic acid and its different linkages. The results demonstrated that the expression level of total glycans increased from middle age to old age. Interestingly, sex-specific N-glycome profiles and alterations were observed. Female mice showed higher level of serum fucosylation and lower level of serum afucosylation than male mice (fucosylation: p < 1.0E-6; afucosylation: p < 1.0E-6). Obviously, higher increase of serum fucosylation level was found in female mice than in male mice from middle age to old age. In addition, the opposite alterations of the afucosylated glycans with α2,3-linked sialic acid and those only with α2,6-linked sialic acid were observed at old age in male mice. These findings suggested that N-glycome could be a valuable target for investigating aging and possible contributors to aging.

5.
Indoor Air ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108019

RESUMO

Household humidification is widely practiced to combat dry indoor air. While the benefits of household humidification are widely perceived, its implications to the indoor air have not been critically appraised. In particular, ultrasonic humidifiers are known to generate fine particulate matter (PM). In this study, we first conducted laboratory experiments to investigate the size, quantity, and chemical composition of PM generated by an ultrasonic humidifier. The mass of PM generated showed a correlation with the total alkalinity of charge water, suggesting that CaCO3 is likely making a major contribution to PM. Ion chromatography analysis revealed a large amount of SO4 2- in PM, representing a previously unrecognized indoor source. Preliminary results of organic compounds being present in humidifier PM are also presented. A whole-house experiment was further conducted at an actual residential house, with five low-cost sensors (AirBeam) monitoring PM in real-time. Operation of a single ultrasonic humidifier resulted in PM2.5 concentrations up to hundreds of µg m-3 , and its influence extended across the entire household. The transport and loss of PM2.5 depended on the rate of air circulation and ventilation. This study emphasizes the need to further investigate the impact of humidifier operation, both on human health and on the indoor atmospheric chemistry, e.g., partitioning of acidic and basic compounds.

6.
Biomed Res Int ; 2020: 5160396, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029511

RESUMO

Oncogene is a special type of genes, which can promote the tumor initiation. Good study on oncogenes is helpful for understanding the cause of cancers. Experimental techniques in early time are quite popular in detecting oncogenes. However, their defects become more and more evident in recent years, such as high cost and long time. The newly proposed computational methods provide an alternative way to study oncogenes, which can provide useful clues for further investigations on candidate genes. Considering the limitations of some previous computational methods, such as lack of learning procedures and terming genes as individual subjects, a novel computational method was proposed in this study. The method adopted the features derived from multiple protein networks, viewing proteins in a system level. A classic machine learning algorithm, random forest, was applied on these features to capture the essential characteristic of oncogenes, thereby building the prediction model. All genes except validated oncogenes were ranked with a measurement yielded by the prediction model. Top genes were quite different from potential oncogenes discovered by previous methods, and they can be confirmed to become novel oncogenes. It was indicated that the newly identified genes can be essential supplements for previous results.

7.
Bioresour Technol ; 318: 124202, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33035945

RESUMO

Pilot-scale saturated vertical flow constructed wetlands (VF-CWs) were established to identify whether T. tubifex has the similar performance in saturated VF-CWs to that in surface flow CWs in improving pollutant removal efficiency (RE). The saturated VF-CWs with T. tubifex achieved REs of 67.3% total nitrogen (TN) and 39.8% chemical oxygen demand (COD), which were significantly higher than treatments without T. tubifex (42.2% TN and 31.4% COD). There existed significant interactions between macrophytes and T. tubifex. T. tubifex greatly improved the dissolved oxygen by increasing the connectivity between layers, and enhanced dehydrogenase activity and fluorescein diacetate. Adding T. tubifex improved the bacterial diversity and relative abundance of both N-cycle bacteria and fermentation bacteria in the biofilms. The improvements of ammonia oxidation and anammox were the main pathways for the increased nitrogen removal by T. tubifex. Therefore, T. tubifex is a useful tool for improving pollutant REs in saturated VF-CWs.


Assuntos
Poluentes Ambientais , Áreas Alagadas , Animais , Análise da Demanda Biológica de Oxigênio , Nitrogênio/análise , Eliminação de Resíduos Líquidos
8.
Transl Oncol ; 14(1): 100875, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32979686

RESUMO

PURPOSE: The presence of microvascular invasion (MVI) is an unfavorable prognostic factor for hepatocellular carcinoma (HCC). This study aimed to construct a nomogram-based preoperative prediction model of MVI, thereby assisting to preoperatively select proper surgical procedures. METHODS: A total of 714 non-metastatic HCC patients undergoing radical hepatectomy were retrospectively selected from Zhongshan Hospital between 2010 and 2018, followed by random assignment into training (N = 520) and validation cohorts (N = 194). Nomogram-based prediction model for MVI risk was constructed by incorporating independent risk factors of MVI presence identified from multivariate backward logistic regression analysis in the training cohort. The performance of nomogram was evaluated by calibration curve and ROC curve. Finally, decision curve analysis (DCA) was used to determine the clinical utility of the nomogram. RESULTS: In total, 503 (70.4%) patients presented MVI. Multivariate analysis in the training cohort revealed that age (OR: 0.98), alpha-fetoprotein (≥400 ng/mL) (OR: 2.34), tumor size (>5 cm) (OR: 3.15), cirrhosis (OR: 2.03) and γ-glutamyl transpeptidase (OR: 1.61) were significantly associated with MVI presence. The incorporation of five risk factors into a nomogram-based preoperative estimation of MVI risk demonstrated satisfactory discriminative capacity, with C-index of 0.702 and 0.690 in training and validation cohorts, respectively. Calibration curve showed good agreement between actual and predicted MVI risks. Finally, DCA revealed the clinical utility of the nomogram. CONCLUSION: The nomogram showed a satisfactory discriminative capacity of MVI risk in HCC patients, and could be used to preoperatively estimate MVI risk, thereby establishing more rational therapeutic strategies.

9.
Blood ; 136(20): 2249-2262, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-32961553

RESUMO

Morphologic interpretation is the standard in diagnosing myelodysplastic syndrome (MDS), but it has limitations, such as varying reliability in pathologic evaluation and lack of integration with genetic data. Somatic events shape morphologic features, but the complexity of morphologic and genetic changes makes clear associations challenging. This article interrogates novel clinical subtypes of MDS using a machine-learning technique devised to identify patterns of cooccurrence among morphologic features and genomic events. We sequenced 1079 MDS patients and analyzed bone marrow morphologic alterations and other clinical features. A total of 1929 somatic mutations were identified. Five distinct morphologic profiles with unique clinical characteristics were defined. Seventy-seven percent of higher-risk patients clustered in profile 1. All lower-risk (LR) patients clustered into the remaining 4 profiles: profile 2 was characterized by pancytopenia, profile 3 by monocytosis, profile 4 by elevated megakaryocytes, and profile 5 by erythroid dysplasia. These profiles could also separate patients with different prognoses. LR MDS patients were classified into 8 genetic signatures (eg, signature A had TET2 mutations, signature B had both TET2 and SRSF2 mutations, and signature G had SF3B1 mutations), demonstrating association with specific morphologic profiles. Six morphologic profiles/genetic signature associations were confirmed in a separate analysis of an independent cohort. Our study demonstrates that nonrandom or even pathognomonic relationships between morphology and genotype to define clinical features can be identified. This is the first comprehensive implementation of machine-learning algorithms to elucidate potential intrinsic interdependencies among genetic lesions, morphologies, and clinical prognostic in attributes of MDS.

10.
Vaccine ; 38(46): 7337-7349, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-32981778

RESUMO

In this study, four codon optimized plasmids (designated as pCAG-optiF-1, 2, -3, and -4) containing modified F genes from the epidemic and virulent NDV genotype VII strain isolated in China that is expected to express the pre-fusion conformation of the F protein were constructed. The expression of these F variants in chicken-derived cells was detected by an indirect immunofluorescence assay and western blot analysis. Two soluble F variants (roptiF-1 and 2) potentially with the pre-fusion conformation were expressed and purified from suspended cells. Vaccination with each of the plasmids as a DNA vaccine conferred partial clinical protection to chicks against NDV. Comparatively, the plasmid pCAG-optiF-2 encoded a soluble protein with a mutant cleavage site and the potential pre-fusion conformation provided better protection than the other plasmids. Further investigation of the combined vaccinations with the plasmid DNA pCAG-optiF-2 prime + protein roptiF-2 boost vaccination strategy elicited more robust immunity, as confirmed by the detection of antibodies against NDV using enzyme-linked immunosorbent assay and virus neutralization assay, as compared to those vaccinated with only the plasmid pCAG-optiF-2 or protein roptiF-2. More importantly, the DNA prime + protein boost vaccination provided more efficacious protection against virulent NDV challenge, as evidenced by the complete clinical protection, reduced viral shedding, and limited virus replication in tissues of the challenge chicks. These results indicated that the pre-fusion conformation of the F protein could be considered as the target immunogen for the development of novel NDV vaccines.

11.
J Proteomics ; 229: 103966, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32891889

RESUMO

N-glycosylation of immunoglobulin G (IgG) has been reported to change in human aging and in some age-related diseases. To further understand the molecular processes that determine these alterations, a detailed examination of individual IgG N-glycans with aging remains required. Mouse is the most commonly used model animal in studies of aging and age-related diseases, and mice have the advantage of relatively controllable genetic and environment variations compared to human. In this study, we systemically investigated the changes in serum IgG N-glycome in C57BL/6 mice during aging at 12 time points (6-80 weeks) via ultraperformance liquid chromatography with fluorescence detection. The study demonstrated several important findings. First, four chromatographic IgG N-glycan peaks were identified for the first time, including a high-mannose glycan, a monoantennary glycan, and two afucosylated glycans. Second, most of the IgG glycan levels changed significantly and presented pronounced gender-related differences from 6 to 12 weeks. Interestingly, all the IgG glycan levels tended to be similar between male and female mice at 12 weeks. Third, the level of fucosylated diantennary glycans containing one N-glycolylneuraminic acid (Neu5Gc)-linked N-acetyllactosamine (LacNAc) decreased gradually and showed a significant negative correlation with age from 24 to 80 weeks (r = -0.716, p < 0.0001), which was not sex-specific. SIGNIFICANCE: More comprehensive profile of murine IgG N-glycans by ultraperformance liquid chromatography with fluorescence detection was shown in this study with four newly identified chromatographic murine IgG N-glycan peaks. The majority of IgG N-glycans showed substantial stage-specific changes and sex-related differences during mouse aging, indicating a strict regulatory mechanism of glycan synthesis. The level of fucosylated diantennary glycans containing one Neu5Gc-linked LacNAc was significantly negatively correlated with age from 24 to 80 weeks, suggesting its great potential as an aging biomarker. The detailed characteristics of IgG N-glycosylation with aging in C57BL/6 mice demonstrated in the present study could provide essential reference data for studying the function and mechanism of IgG glycosylation in age-related researches based on C57BL/6 mouse models.

12.
Oxid Med Cell Longev ; 2020: 9270107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963706

RESUMO

Endoplasmic reticulum (ER) stress is closely associated with atherosclerosis and related cardiovascular diseases (CVDs). It occurs due to various pathological factors that interfere with ER homeostasis, resulting in the accumulation of unfolded or misfolded proteins in the ER lumen, thereby causing ER dysfunction. Here, we discuss the role of ER stress in different types of cells in atherosclerotic lesions. This discussion includes the activation of apoptotic and inflammatory pathways induced by prolonged ER stress, especially in advanced lesional macrophages and endothelial cells (ECs), as well as common atherosclerosis-related ER stressors in different lesional cells, which all contribute to the clinical progression of atherosclerosis. In view of the important role of ER stress and the unfolded protein response (UPR) signaling pathways in atherosclerosis and CVDs, targeting these processes to reduce ER stress may be a novel therapeutic strategy.

13.
Environ Sci Technol ; 54(19): 12484-12492, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-32936620

RESUMO

Photochemical processing taking place in atmospheric aqueous phases serves as both a source and a sink of organic compounds. In aqueous environments, acid-base chemistry and, by extension, aqueous-phase pH, are an important yet often neglected factors to consider when investigating the kinetics of organic compounds. We have investigated the aqueous-phase OH-oxidation of pinic acid, cis-pinonic acid, limononic acid, and formic acid (FA) as a function of pH. We have also extended our studies to other organic acids (OAs) present in the water-soluble fraction of secondary organic aerosol (SOA) arising from the ozonolysis of α-pinene. Although all the OAs exhibited larger OH reactivities at pH 10, the pH dependence was dramatically different between FA, the smallest OA, and those that contained more than eight carbons. A kinetic box model was also employed to characterize our photoreactor and to provide confidence to our results. Our finding shows that the atmospheric lifetimes of small OAs (e.g., FA) are highly sensitive to cloud water pH. However, those of larger OAs and many other OAs in α-pinene SOA are affected to a much less extent. These results are of great importance for the simplification of cloud water chemistry models.

14.
J Environ Manage ; 272: 111109, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32854897

RESUMO

Heavy metals (HM) pollution is a major limitation to the application of composting products. Therefore, mitigating the toxicity of HM has attracted wide attention during composting. The toxicity of HM is mainly acted on microorganisms during composting, and the toxicity of different HM speciation is obviously various. There are many pathways to change the speciation to reduce the toxicity during composting. Therefore, in this review, the speciation distribution, toxicity mechanism and remediation ways of HM during composting were discussed in order to better solve HM pollution. The microbial remediation technology holds enormous potential to remediate for HM without damaging composting, however, it is hard to extract HM. The innovation of this review was to outline microbial remediation strategies for HM during composting based on two mechanisms of microbial remediation: extracellular adsorption and intracellular sequestration, to solve the problem how to extract microbial agents from the compost. Ultimately, a novel theoretical method of microbial remediation was proposed to remove HM from the compost.


Assuntos
Compostagem , Metais Pesados/análise , Poluentes do Solo/análise , Poluição Ambiental , Solo
15.
Biomed Res Int ; 2020: 8916729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851091

RESUMO

AURKA, a cell cycle-regulated kinase, is associated with malignant transformation and progression in many cancer types. We analyzed the expression change of AURKA in pan-cancer and its effect on the prognosis of cancer patients using the TCGA dataset. We revealed that AURKA was extensively elevated and predicted a poor prognosis in most of the detected cancer types, with an exception in colon cancer. AURKA was elevated in colon cancer, but the upregulation of AURKA indicated better outcomes of colon cancer patients. Then we revealed that undermethylation of the AURKA gene and several transcription factors contributed to the upregulation of AURKA in colon cancer. Moreover, we demonstrated that AURKA overexpression promoted the death of colon cancer cells induced by Oxaliplatin, whereas knockdown of AURKA significantly weakened the chemosensitivity of colon cancer cells to Oxaliplatin. Mechanistically, AURKA inhibited DNA damage response by suppressing the expression of various DNA damage repair genes in a TP53-dependent manner, which can partly explain that ARUKA is associated with a beneficial outcome of colon cancer. This study provided a possibility to use AURKA as a biomarker to predict the chemosensitivity of colon cancer to platinum in the clinic.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32803949

RESUMO

In this work, a novel heterojunction catalyst was constructed by introducing Ti3C2 MXene quantum dots (QDs) into SiC. The Ti3C2 MXene QDs/SiC composite showed 74.6% efficiency in NO pollutant removal under visible light irradiation, which is 3.1 and 3.7 times higher than those of the bare Ti3C2 MXene quantum dots and SiC, respectively. The Ti3C2 MXene quantum dots existing in SiC can function as a channel for electron and hole transfer. The enhanced visible light absorption, increased superoxide radical, and strong oxidization ability endow the Ti3C2 MXene QDs/SiC composite with a superior photocatalytic performance for NOx removal. The increased superoxide radical formation and enhanced oxidization ability of Ti3C2 MXene QDs/SiC were demonstrated by theoretical calculations. The robust stability in both photocatalytic performance and crystal structures was revealed in the Ti3C2 MXene QDs/SiC composite using the cycling test, transient photocurrent response, XRD, and TG.

17.
Psych J ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32812394

RESUMO

Despite the obvious power of the money motive, money has received little attention from psychologists' writing about human motivation. Considering China's transition from its high material deprivation of several decades ago to its current rapidly developing economy, this study aimed to examine how the motives for making money affect life satisfaction through the analysis of a sample of 5,911 participants. The results were somewhat different from previous studies: all the basic motives, self-integrated motives, and non-integrated motives for making money were positively correlated with life satisfaction. We argue that, as the tool/drug theory of money states, money gives people immediate reward, like a drug. More precisely, our findings suggest that belongingness and meaningfulness of life mediate the relationship between motives for making money and life satisfaction. Based on the tool/drug theory, money can be exchanged for social status and can be used to pursue social display and social protection. Motives for making money can bring a sense of belongingness and meaningfulness of life in a large pay-disparity context. Together, these findings extend our understanding of the tool/drug theory and the cultural attributes of money. A longitudinal study is urgently needed in the future to explore the duration of the "drug effect."

18.
mBio ; 11(4)2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32817100

RESUMO

Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a representative gas-fermenting bacterium, Clostridium ljungdahlii, we revealed a novel regulatory mechanism that employs both the lysine acetylation and transcriptional regulation systems to interactively control CO2 fixation, a key biological process for utilizing this one-carbon gas. A dominant lysine acetyltransferase/deacetylase system, At2/Dat1, was identified and found to regulate FDH1 (formate dehydrogenase responsible for CO2 fixation) activity via a crucial acetylation site (lysine-29). Notably, the global transcription factor CcpA was also shown to be regulated by At2/Dat1; in turn, CcpA could directly control At2 expression, thus indicating an unreported interaction mode between the acetylation system and transcription factors. Moreover, CcpA was observed to negatively regulate FDH1 expression, which, when combined with At2/Dat1, leads to the collaborative regulation of this enzyme. Based on this concept, we reconstructed the regulatory network related to FDH1, realizing significantly increased CO2 utilization by C. ljungdahlii IMPORTANCE Microbial CO2 fixation and conversion constitute a potential solution to both utilization of greenhouse gas or industrial waste gases and sustainable production of bulk chemicals and fuels. Autotrophic gas-fermenting bacteria play central roles in this bioprocess. This study provides new insights regarding the metabolic regulatory mechanisms underlying CO2 reduction in Clostridium ljungdahlii, a representative gas-fermenting bacterium. A critical formate dehydrogenase (FDH1) responsible for fixing CO2 and a dominant reversible lysine acetylation system, At2/Dat1, were identified. Furthermore, FDH1 was found to be interactively regulated by both the At2/Dat1 system and the global transcriptional factor CcpA, and the two regulatory systems are mutually restricted. Reconstruction of this multilevel metabolic regulatory module led to improved CO2 metabolism by C. ljungdahlii These findings not only substantively expand our understanding but also provide a potentially useful metabolic engineering strategy for microbial carbon fixation.

19.
Sci Adv ; 6(31): eaay9131, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32789167

RESUMO

Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define the vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated the mechanism of piperlongumine, a small molecule identified in a chemical library screen to specifically target cancer cells with a hyperactive mTORC1 phenotype. Sensitivity to piperlongumine was dependent on its ability to suppress RUVBL1/2-TTT, a complex involved in chromatin remodeling and DNA repair. Cancer cells with high mTORC1 activity are subjected to higher levels of DNA damage stress via c-Myc and displayed an increased dependency on RUVBL1/2 for survival and counteracting genotoxic stress. Examination of clinical cancer tissues also demonstrated that high mTORC1 activity was accompanied by high RUVBL2 expression. Our findings reveal a previously unknown role for RUVBL1/2 in cell survival, where it acts as a functional chaperone to mitigate stress levels induced in the mTORC1-Myc-DNA damage axis.

20.
Cell Rep ; 32(4): 107952, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32726617

RESUMO

A certain number of epithelial cells in intestinal crypts are DNA damage resistant and contribute to regeneration. However, the cellular mechanism underlying intestinal regeneration remains unclear. Using lineage tracing, we show that cells marked by an Msi1 reporter (Msi1+) are right above Lgr5high cells in intestinal crypts and exhibit DNA damage resistance. Single-cell RNA sequencing reveals that the Msi1+ cells are heterogeneous with the majority being intestinal stem cells (ISCs). The DNA damage-resistant subpopulation of Msi1+ cells is characterized by low-to-negative Lgr5 expression and is more rapidly cycling than Lgr5high radiosensitive crypt base columnar stem cells (CBCs). This enables an efficient repopulation of the intestinal epithelium at early stage when Lgr5high cells are not emerging. Furthermore, relative to CBCs, Msi1+ cells preferentially produce Paneth cells during homeostasis and upon radiation repair. Together, we demonstrate that the DNA damage-resistant Msi1+ cells are cycling ISCs that maintain and regenerate the intestinal epithelium.

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