دورية أكاديمية
Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing
| العنوان: | Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing |
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| المؤلفون: | Xing, Qiao Rui, El Farran, C. A., Gautam, P., Chuah, Y. S., Warrier, T., Toh, C. X. D., Kang, N. Y., Sugii, S., Chang, Y. T., Xu, J., Collins, J. J., Daley, G. Q., Li, H., Zhang, Li-Feng, Loh, Y. H. |
| المساهمون: | School of Biological Sciences |
| سنة النشر: | 2020 |
| المجموعة: | DR-NTU (Digital Repository at Nanyang Technological University, Singapore) |
| مصطلحات موضوعية: | Science::Biological sciences, Chromosomes, Machinery |
| الوصف: | Cellular reprogramming suffers from low efficiency especially for the human cells. To deconstruct the heterogeneity and unravel the mechanisms for successful reprogramming, we adopted single-cell RNA sequencing (scRNA-Seq) and single-cell assay for transposase-accessible chromatin (scATAC-Seq) to profile reprogramming cells across various time points. Our analysis revealed that reprogramming cells proceed in an asynchronous trajectory and diversify into heterogeneous subpopulations. We identified fluorescent probes and surface markers to enrich for the early reprogrammed human cells. Furthermore, combinatory usage of the surface markers enabled the fine segregation of the early-intermediate cells with diverse reprogramming propensities. scATAC-Seq analysis further uncovered the genomic partitions and transcription factors responsible for the regulatory phasing of reprogramming process. Binary choice between a FOSL1 and a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Together, our study illuminates the multitude of diverse routes transversed by individual reprogramming cells and presents an integrative roadmap for identifying the mechanistic part list of the reprogramming machinery. ; Agency for Science, Technology and Research (A*STAR) ; Ministry of Education (MOE) ; Ministry of Health (MOH) ; National Medical Research Council (NMRC) ; National Research Foundation (NRF) ; Published version ; H.L. is supported by the NIH (AG056318, AG61796, and CA208517), the Glenn Foundation for Medical Research, Mayo Clinic Center for Biomedical Discovery, Center for Individualized Medicine, Mayo Clinic Cancer Center, and the David F. and Margaret T. Grohne Cancer Immunology and Immunotherapy Program. L.F.Z. is supported by the Singapore Ministry of Education Academic Research Fund (MOE2015-T2-1-093) and Singapore National Research Foundation under its Cooperative Basic Research Grant administered by the Singapore Ministry of Health’s National Medical Research Council ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2375-2548 |
| العلاقة: | MOE2015-T2-1-093; NMRC/CBRG/0092/2015; NRFI2018-02; Science Advances; Xing, Q. R., El Farran, C. A., Gautam, P., Chuah, Y. S., Warrier, T., Toh, C. X. D., . . . Loh, Y. H. (2020). Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing. Science Advances, 6(37), eaba1190-. doi:10.1126/sciadv.aba1190; https://hdl.handle.net/10356/145388Test; 37 |
| DOI: | 10.1126/sciadv.aba1190 |
| الإتاحة: | https://doi.org/10.1126/sciadv.aba1190Test https://hdl.handle.net/10356/145388Test |
| حقوق: | © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). |
| رقم الانضمام: | edsbas.D6440814 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 23752548 |
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| DOI: | 10.1126/sciadv.aba1190 |