期刊
CELL STEM CELL
卷 25, 期 1, 页码 149-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2019.05.020
关键词
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资金
- NIH [HG06272]
- NIH BD2K Fellowship [T32 CA201159]
- NIH F31 Fellowship [HG008912]
- UNC Integrative Vascular Biology Training Grant [NIH T32 HL069768]
- NIH/NHLBI [R01HL139880, R01HL128331, R01HL144551]
- AHA [18TPA34180058]
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-responseassociated 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.
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