Single-Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming. Cell Stem Cell 2019 Jul 03;25(1):149-164.e9
Date
06/25/2019Pubmed ID
31230860Pubmed Central ID
PMC6684137DOI
10.1016/j.stem.2019.05.020Scopus ID
2-s2.0-85068031202 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
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 LAuthor
Ziqing Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Differentiation
Cell Lineage
Cellular Reprogramming
Cellular Reprogramming Techniques
Fibroblasts
Humans
Myocytes, Cardiac
Sequence Analysis, RNA
Single-Cell Analysis
Transcriptome
