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

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 normal...

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Veröffentlicht in:Cell stem cell Jg. 25; H. 1; S. 149
Hauptverfasser: Zhou, Yang, Liu, Ziqing, Welch, Joshua D, Gao, Xu, Wang, Li, Garbutt, Tiffany, Keepers, Benjamin, Ma, Hong, Prins, Jan F, Shen, Weining, Liu, Jiandong, Qian, Li
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 03.07.2019
Schlagworte:
Animals
Cell Differentiation
Cell Lineage
Cellular Reprogramming
Cellular Reprogramming Techniques
Fibroblasts - physiology
Humans
Myocytes, Cardiac - physiology
Sequence Analysis, RNA
Single-Cell Analysis - methods
Transcriptome
CELL reprogramming
cell fate index
iCM
SLICER
fibroblast
RNA velocity
single-cell RNA-seq
ISSN:1875-9777, 1875-9777
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2019.05.020