Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Oct 6

PMID 30290179

Citations 135

Authors

Clayton E Friedman

Quan Nguyen

Samuel W Lukowski

Abbigail Helfer

Han Sheng Chiu

Jason Miklas

Shiri Levy

Shengbao Suo

Jing-Dong Jackie Han

Pierre Osteil

Guangdun Peng

Naihe Jing

Greg J Baillie

Anne Senabouth

Angelika N Christ

Timothy J Bruxner

Charles E Murry

Emily S Wong

Jun Ding

Yuliang Wang

James Hudson

Hannele Ruohola-Baker

Ziv Bar-Joseph

Patrick P L Tam

Joseph E Powell

Nathan J Palpant

Affiliations

Soon will be listed here.

Abstract

Cardiac differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic gene regulatory networks during stepwise fate transitions but often generates immature cell types that do not fully recapitulate properties of their adult counterparts, suggesting incomplete activation of key transcriptional networks. We performed extensive single-cell transcriptomic analyses to map fate choices and gene expression programs during cardiac differentiation of hPSCs and identified strategies to improve in vitro cardiomyocyte differentiation. Utilizing genetic gain- and loss-of-function approaches, we found that hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation. This study therefore provides a key transcriptional roadmap of in vitro cardiac differentiation at single-cell resolution, revealing fundamental mechanisms underlying heart development and differentiation of hPSC-derived cardiomyocytes.

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