RT Journal Article
SR Electronic
T1 Diversification of Reprogramming Trajectories Revealed by Parallel Single-cell Transcriptome and Chromatin Accessibility Sequencing
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 829853
DO 10.1101/829853
A1 Qiaorui Xing
A1 Chadi El Farran
A1 Pradeep Gautam
A1 Yu Song Chuah
A1 Tushar Warrier
A1 Cheng-Xu Delon Toh
A1 Nam-Young Kang
A1 Shigeki Sugii
A1 Young-Tae Chang
A1 Jian Xu
A1 James Collins
A1 George Daley
A1 Hu Li
A1 Li-Feng Zhang
A1 Yuin-Han Loh
YR 2019
UL http://biorxiv.org/content/early/2019/11/04/829853.abstract
AB To unravel the mechanism of human cellular reprogramming process at single-cell resolution, we performed parallel scRNA-Seq and scATAC-Seq analysis. Our analysis reveals that the cells undergoing reprogramming proceed in an asynchronous trajectory and diversify into heterogeneous sub-populations. BDD2-C8 fluorescent probe staining and negative staining for CD13, CD44 and CD201 markers, could enrich for the GDF3+ early reprogrammed cells. Combinatory usage of the surface markers enables 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 or a TEAD4-centric regulatory network determines the outcome of a successful reprogramming. Altogether, 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.