MYOCD is Required for Cardiomyocyte-like Cells Induction from Human Urine Cells and Fibroblasts Through Remodeling Chromatin.
Xiangyu ZhangLijun ChenXingnan HuangHuan ChenBaomei CaiYue QinYating ChenSihua OuXiaoxi LiZichao WuZiyu FengMengying ZengWenjing GuoHeying LiChunhua ZhouShengyong YuMengjie PanJing LiuKai KangShangtao CaoDuanqing PeiPublished in: Stem cell reviews and reports (2022)
Despite direct reprogramming of human cardiac fibroblasts into induced cardiomyocytes (iCM) holds great potential for heart regeneration, the mechanisms are poorly understood. Whether other human somatic cells could be reprogrammed into cardiomyocytes is also unknown. Here, we report human urine cells (hUCs) could be converted into CM-like cells from different donors and the related chromatin accessibility dynamics (CAD) by assay for transposase accessible chromatin(ATAC)-seq. hUCs transduced by MEF2C, TBX5, MESP1 and MYOCD but without GATA4 expressed multiple cardiac specific genes, exhibited Ca 2+ oscillation potential and sarcomeric structures, and contracted synchronously in coculture with mouse CM. Additionally, we found that MYOCD is required for both closing and opening critical loci, mainly by hindering the opening of loci enriched with motifs for the TEAD and AP1 family and promoting the closing of loci enriched with ETS motifs. These changes differ partially from CAD observed during iCM induction from human fibroblasts. Collectively, our study offers one practical platform for iCM generation and insights into mechanisms for iCM fate determination.
Keyphrases
- endothelial cells
- genome wide
- transcription factor
- induced apoptosis
- induced pluripotent stem cells
- dna damage
- coronary artery disease
- heart failure
- left ventricular
- cell cycle arrest
- oxidative stress
- high throughput
- hypertrophic cardiomyopathy
- angiotensin ii
- risk assessment
- copy number
- drug induced
- protein kinase
- liquid chromatography