Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators  

作　　者：Jianglin Wang Xueyan Jiang Lixin Zhao Shengjia Zuo Xiantong Chen Lingmin Zhang Zhongxiao Lin Xiaoya Zhao Yuyan Qin Xinke Zhou Xi-Yong Yu 

机构地区：[1]Key Laboratory of Molecular Target&Clinical Pharmacology and the State Key Laboratory of Respiratory Disease,School of Pharmaceutical Sciences&the Fifth Affiliated Hospital,Guangzhou Medical University,Guangzhou 511436,China

出　　处：《Acta Pharmaceutica Sinica B》2020年第2期313-326,共14页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(grant numbers 81330007 and U1601227 to XiYong Yu,81700382 to Lingmin Zhang);the Science andTechnology Programs of Guangdong Province(grant numbers20158020225006 to Xi-Yong Yu,China).

摘　　要：Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types.Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells(iCPCs).CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity.Here we show lineage reprogramming to iCPCs through a dead Cas9(dCas9)-based transcription activation system.Targeted and robust activation of endogenous cardiac factors,including GATA4,HAND2,MEF2 C and TBX5(G,H,M and T;GHMT),can reprogram human fibroblasts toward iCPCs.The iCPCs show potentials to differentiate into cardiomyocytes,smooth muscle cells and endothelial cells in vitro.Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming.Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling,drug discovery and individualized cardiac cell therapy.

关 键 词：LINEAGE REPROGRAMMING Human FORESKIN FIBROBLASTS INDUCED CARDIAC progenitor cells CRISPR/Cas9 SAM CARDIAC transcription factors 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]