論文

査読有り
2016年4月

Cardiac mesenchymal progenitors differentiate into adipocytes via Klf4 and c-Myc

CELL DEATH & DISEASE
  • D. Kami
  • ,
  • T. Kitani
  • ,
  • T. Kawasaki
  • ,
  • S. Gojo

7
開始ページ
e2190
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/cddis.2016.31
出版者・発行元
NATURE PUBLISHING GROUP

Direct reprogramming of differentiated cells to pluripotent stem cells has great potential to improve our understanding of developmental biology and disorders such as cancers, and has implications for regenerative medicine. In general, the effects of transcription factors (TFs) that are transduced into cells can be influenced by pre-existing transcriptional networks and epigenetic modifications. However, previous work has identified four key TFs, Oct4, Sox2, Klf4 and c-Myc, which can reprogram various differentiated cells to generate induced pluripotent stem cells. Here, we show that in the heart, the transduction of cardiac mesenchymal progenitors (CMPs) with Klf4 and c-Myc (KM) was sufficient to drive the differentiation of these cells into adipocytes without the use of adipogenic stimulation cocktail, that is, insulin, 3-isobutyl-1-methylxanthine (IBMX) and dexamethasone. KM-transduced CMPs exhibited a gradually increased expression of adipogenic-related genes, such as C/Ebpa, Ppar gamma and Fabp4, activation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway, inactivation of the cell cycle-related pathway and formation of cytoplasmic lipid droplets within 10 days. In contrast, NIH3T3 fibroblasts, 3T3-L1 preadipocytes, and bone marrow-derived mesenchymal stem cells transduced with KM did not differentiate into adipocytes. Both in vitro and in vivo cardiac ischemia reperfusion injury models demonstrated that the expression of KM genes sharply increased following a reperfusion insult. These results suggest that ectopic adipose tissue formation in the heart following myocardial infarction results from CMPs that express KM following a stress response.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1038/cddis.2016.31
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27077806
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000375277600017&DestApp=WOS_CPL

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