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  • 标题:Direct reprogramming of adult adipose-derived regenerative cells toward cardiomyocytes using six transcriptional factors
  • 本地全文:下载
  • 作者:Shingo Narita ; Kazumasa Unno ; Katsuhiro Kato
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:7
  • 页码:1-21
  • DOI:10.1016/j.isci.2022.104651
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummaryIt is widely accepted that adipose-derived regenerative cells (ADRCs) can differentiate into mesodermal lineage cells. However, reprogramming adult ADRCs into mature cardiomyocytes is challenging. We investigated the induction of myocardial differentiation in ADRCs via direct reprogramming using lentiviral gene transfer. First, we identified candidate transcriptional factors by performing RNA sequencing and ultimately confirmed that the combination of six unique factors (Baf60c,Gata4,Gata6,Klf15,Mef2a, andMyocd) could efficiently express enhanced green fluorescent protein (GFP) in ADRCs isolated from adult alpha-myosin heavy chain promoter-driven GFP transgenic mice. The GFP-positive ADRCs induced by six factors (6F-ADRCs) expressed multiple cardiac genes and revealed cardiac differentiation in bioinformatic analysis. Moreover, injection of 6F-ADRCs into acute myocardial infarcted tissuesin vivoresulted in the improvement of survival rate, fractional shortening, and reduction of infarction scar area. This study provides an alternative method for direct reprogramming of adult ADRCs into cardiomyocytes.Graphical abstractDisplay OmittedHighlights•Six transcriptional factors can differentiate ADRCs (6F-ADRCs) into cardiomyocytes•Bioinformatic analysis shows that 6F-ADRCs express multiple cardiac genes•Gene Ontology analysis indicates 6F-ADRCs toward cardiac differentiation•6F-ADRCs have potential for cardiac regeneration inin vivotransplantation modelCell biology, Stem cells research, Molecular biology
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