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

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jun 25

PMID 31230860

Citations 74

Authors

Yang Zhou

Ziqing Liu

Joshua D Welch

Xu Gao

Li Wang

Tiffany Garbutt

Benjamin Keepers

Hong Ma

Jan F Prins

Weining Shen

Jiandong Liu

Li Qian

Affiliations

Soon will be listed here.

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.

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