Renikunta Harsha V, Lazarow Katina, Gong Yiqi, Shukla Praphulla Chandra, Nageswaran Vanasa, Giral Hector, Kratzer Adelheid, Opitz Lennart, Engel Felix B, Haghikia Arash, Costantino Sarah, Paneni Francesco, von Kries Jens Peter, Streckfuss-Bömeke Katrin, Landmesser Ulf, Jakob Philipp
Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care, Hindenburgdamm 30, 12203 Berlin, Germany.
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany.
iScience. 2023 Apr 8;26(5):106593. doi: 10.1016/j.isci.2023.106593. eCollection 2023 May 19.
Ischemic cardiomyopathy, driven by loss of cardiomyocytes and inadequate proliferative response, persists to be a major global health problem. Using a functional high-throughput screening, we assessed differential proliferative potential of 2019 miRNAs after transient hypoxia by transfecting both miR-inhibitor and miR-mimic libraries in human iPSC-CM. Whereas miR-inhibitors failed to enhance EdU uptake, overexpression of 28 miRNAs substantially induced proliferative activity in hiPSC-CM, with an overrepresentation of miRNAs belonging to the primate-specific C19MC-cluster. Two of these miRNAs, miR-515-3p and miR-519e-3p, increased markers of early and late mitosis, indicative of cell division, and substantially alter signaling pathways relevant for cardiomyocyte proliferation in hiPSC-CM.
缺血性心肌病由心肌细胞丢失和增殖反应不足驱动，仍然是一个主要的全球健康问题。通过功能高通量筛选，我们通过在人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）中转染miR抑制剂和miR模拟物文库，评估了2019种微小RNA（miRNA）在短暂缺氧后的增殖潜力差异。虽然miR抑制剂未能增强5-乙炔基-2'-脱氧尿苷（EdU）摄取，但28种miRNA的过表达显著诱导了hiPSC-CM中的增殖活性，其中属于灵长类特异性C19MC簇的miRNA占比过高。其中两种miRNA，即miR-515-3p和miR-519e-3p，增加了早期和晚期有丝分裂的标志物，表明细胞分裂，并显著改变了hiPSC-CM中与心肌细胞增殖相关的信号通路。
