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In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals

文献类型：期刊论文

作者Chen, Zi-yang4,5; Ji, Si-jia3,4,5; Huang, Chen-wen5; Tu, Wan-zhi3,4,5; Ren, Xin-yue4,5; Guo, Ren2,5; Xie, Xin1,2,3,4,5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2024-06-18
页码10
关键词cardiac transdifferentiation in situ transdifferentiation small molecules cardiomyocytes fibroblasts in vivo transdifferentiation
ISSN号1671-4083
DOI10.1038/s41401-024-01308-6
通讯作者Xie, Xin(xxie@simm.ac.cn)
英文摘要Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration.
WOS关键词PLURIPOTENT STEM-CELLS ; REGENERATION ; GENERATION ; MICRORNAS ; MYOCYTES ; STATE
资助项目Ministry of Science and Technology of China[2022YFA1104700] ; Ministry of Science and Technology of China[2022ZD0204700] ; National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[82330113] ; National Natural Science Foundation of China[31900518] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2022280] ; Fundamental Research Projects of Science & Technology Innovation and Development Plan in Yantai City[2023JCYJ063] ; Taishan Scholars Program
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001250425000001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/312059]  
专题新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
4.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Zi-yang,Ji, Si-jia,Huang, Chen-wen,et al. In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals[J]. ACTA PHARMACOLOGICA SINICA,2024:10.
APA Chen, Zi-yang.,Ji, Si-jia.,Huang, Chen-wen.,Tu, Wan-zhi.,Ren, Xin-yue.,...&Xie, Xin.(2024).In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals.ACTA PHARMACOLOGICA SINICA,10.
MLA Chen, Zi-yang,et al."In situ reprogramming of cardiac fibroblasts into cardiomyocytes in mouse heart with chemicals".ACTA PHARMACOLOGICA SINICA (2024):10.

入库方式： OAI收割

来源：上海药物研究所

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