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Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming.

Abstract：

:Direct cellular reprogramming provides a powerful platform to study cell plasticity and dissect mechanisms underlying cell fate determination. Here, we report a single-cell transcriptomic study of human cardiac (hiCM) reprogramming that utilizes an analysis pipeline incorporating current data normalization methods, multiple trajectory prediction algorithms, and a cell fate index calculation we developed to measure reprogramming progression. These analyses revealed hiCM reprogramming-specific features and a decision point at which cells either embark on reprogramming or regress toward their original fibroblast state. In combination with functional screening, we found that immune-response-associated DNA methylation is required for hiCM induction and validated several downstream targets of reprogramming factors as necessary for productive hiCM reprograming. Collectively, this single-cell transcriptomics study provides detailed datasets that reveal molecular features underlying hiCM determination and rigorous analytical pipelines for predicting cell fate conversion.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Zhou Y,Liu Z,Welch JD,Gao X,Wang L,Garbutt T,Keepers B,Ma H,Prins JF,Shen W,Liu J,Qian L

doi

10.1016/j.stem.2019.05.020

subject

Has Abstract

pub_date

2019-07-03 00:00:00

pages

149-164.e9

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(19)30224-3

journal_volume

25

pub_type

杂志文章

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