Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming. Cell Stem Cell 2019 Jul 03;25(1):149-164.e9

Date

06/25/2019

Pubmed ID

31230860

Pubmed Central ID

PMC6684137

DOI

10.1016/j.stem.2019.05.020

Scopus ID

2-s2.0-85068031202   57 Citations

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.

Author List

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

Author

Ziqing Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cell Lineage
Cellular Reprogramming
Cellular Reprogramming Techniques
Fibroblasts
Humans
Myocytes, Cardiac
Sequence Analysis, RNA
Single-Cell Analysis
Transcriptome