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Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures.

Abstract：

:Direct cardiac reprogramming holds great potential for regenerative medicine. However, it remains inefficient, and induced cardiomyocytes (iCMs) generated in vitro are less mature than those in vivo, suggesting that undefined extrinsic factors may regulate cardiac reprogramming. Previous in vitro studies mainly used hard polystyrene dishes, yet the effect of substrate rigidity on cardiac reprogramming remains unclear. Thus, we developed a Matrigel-based hydrogel culture system to determine the roles of matrix stiffness and mechanotransduction in cardiac reprogramming. We found that soft matrix comparable with native myocardium promoted the efficiency and quality of cardiac reprogramming. Mechanistically, soft matrix enhanced cardiac reprogramming via inhibition of integrin, Rho/ROCK, actomyosin, and YAP/TAZ signaling and suppression of fibroblast programs, which were activated on rigid substrates. Soft substrate further enhanced cardiac reprogramming with Sendai virus vectors via YAP/TAZ suppression, increasing the reprogramming efficiency up to ∼15%. Thus, mechanotransduction could provide new targets for improving cardiac reprogramming.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Kurotsu S,Sadahiro T,Fujita R,Tani H,Yamakawa H,Tamura F,Isomi M,Kojima H,Yamada Y,Abe Y,Murakata Y,Akiyama T,Muraoka N,Harada I,Suzuki T,Fukuda K,Ieda M

doi

10.1016/j.stemcr.2020.07.022

subject

Has Abstract

pub_date

2020-09-08 00:00:00

pages

612-628

issue

3

issn

2213-6711

pii

S2213-6711(20)30299-X

journal_volume

15

pub_type

杂志文章

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