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Cited 27 time in webofscience Cited 28 time in scopus
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Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing SCIE SCOPUS

Title
Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing
Authors
Xing, Q. R.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, L. F.Loh, Y. H.
Date Issued
2020-09
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
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.
URI
https://oasis.postech.ac.kr/handle/2014.oak/107146
DOI
10.1126/sciadv.aba1190
ISSN
2375-2548
Article Type
Article
Citation
SCIENCE ADVANCES, vol. 6, no. 37, 2020-09
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