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Chang, Young Tae
복잡계 자기조립 연구단
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Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing

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Title
Diversification of reprogramming trajectories revealed by parallel single-cell transcriptome and chromatin accessibility sequencing
Author(s)
Q. R. Xing; C. A. El Farran; P. Gautam; Y. S. Chuah; T. Warrier; C. X. D. Toh; N. Y. Kang; S. Sugii; Young Tae Chang; J. Xu; J. J. Collins; G. Q. Daley; H. Li; L. F. Zhang; Y. H. Loh
Subject
SYSTEMATIC IDENTIFICATION, ; INDUCED PLURIPOTENCY, ; HUMAN FIBROBLASTS, ; STEM-CELLS, ; REGULATORS, ; INDUCTION, ; DYNAMICS, ; BINDING, ; FATE
Publication Date
2020-09
Journal
SCIENCE ADVANCES, v.6, no.37, pp.eaba1190
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
© 2020 The Authors. 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://pr.ibs.re.kr/handle/8788114/7639
DOI
10.1126/sciadv.aba1190
ISSN
2375-2548
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
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