MicroRNA-199a induces differentiation of induced pluripotent stem cells into endothelial cells by targeting sirtuin 1

Mol Med Rep. 2015 Sep;12(3):3711-3717. doi: 10.3892/mmr.2015.3845. Epub 2015 May 25.

Abstract

The ability to reprogram induced pluripotent stem (iPS) cells from somatic cells may facilitate significant advances in regenerative medicine. MicroRNAs (miRNAs) are involved in a number of core biological processes, including cardiogenesis, hematopoietic lineage differentiation and oncogenesis. An improved understanding of the complex molecular signals that are required for the differentiation of iPS cells into endothelial cells (ECs) may allow specific targeting of their activity in order to enhance cell differentiation and promote tissue regeneration. The present study reports that miR‑199a is involved in EC differentiation from iPS cells. Augmented expression of miR‑199a was detected during EC differentiation, and reached higher levels during the later stages of this process. Furthermore, miR‑199a inhibited the differentiation of iPS cells into smooth muscle cells. Notably, sirtuin 1 was identified as a target of miR‑199a . Finally, the ability of miR‑199a to induce angiogenesis was evaluated in vitro, using Matrigel plugs assays. This may indicate a novel function for miR‑199a as a regulator of the phenotypic switch during vascular cell differentiation. The present study provides support to the notion that with an understanding of the molecular mechanisms underlying vascular cell differentiation, stem cell regenerative therapy may ultimately be developed as an effective treatment for cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mice
  • MicroRNAs / genetics*
  • Neovascularization, Physiologic*
  • Sirtuin 1 / genetics*

Substances

  • MicroRNAs
  • Mirn199 microRNA, mouse
  • Sirtuin 1