研究表明，两个微RNA，即miR-145 和 miR-143，存在于小鼠胚胎的多能心脏先祖细胞中。

miR-145是由心肌蛋白诱导的成年成纤维细胞向平滑肌细胞内的重新编程所必需的，并且足以诱导神经冠干细胞分化成“血管平滑肌细胞”（VSMC）。miR-145 和 miR-143一起以一个转录因子网络为目标，来促进平滑肌细胞的分化和抑制其增殖。这些发现提供的证据表明，微RNA能够起开关的作用，引导细胞向某个特定的体系分化。另外，miR-145 和 miR-143在调控VSMC的分化表现型和增殖表现型中所起作用在很多血管类疾病中可能是有关系的，因为VSMC在这两种状态之间的振荡有助于血管闭塞。（生物谷Bioon.com）

生物谷推荐原始出处：

Nature 460, 705-710 (6 August 2009) | doi:10.1038/nature08195

miR-145 and miR-143 regulate smooth muscle cell fate and plasticity

Kimberly R. Cordes1,2,3, Neil T. Sheehy1,2,3, Mark P. White1,2,3, Emily C. Berry1,2,3, Sarah U. Morton1,2,3, Alecia N. Muth1,2,3, Ting-Hein Lee4, Joseph M. Miano4, Kathryn N. Ivey1,2,3 & Deepak Srivastava1,2,3

1 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
2 Department of Pediatrics, University of California, San Francisco, California 94543, USA
3 Department of Biochemistry & Biophysics, University of California, San Francisco, California 94143, USA
4 Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA

MicroRNAs (miRNAs) are regulators of myriad cellular events, but evidence for a single miRNA that can efficiently differentiate multipotent stem cells into a specific lineage or regulate direct reprogramming of cells into an alternative cell fate has been elusive. Here we show that miR-145 and miR-143 are co-transcribed in multipotent murine cardiac progenitors before becoming localized to smooth muscle cells, including neural crest stem-cell-derived vascular smooth muscle cells. miR-145 and miR-143 were direct transcriptional targets of serum response factor, myocardin and Nkx2-5 (NK2 transcription factor related, locus 5) and were downregulated in injured or atherosclerotic vessels containing proliferating, less differentiated smooth muscle cells. miR-145 was necessary for myocardin-induced reprogramming of adult fibroblasts into smooth muscle cells and sufficient to induce differentiation of multipotent neural crest stem cells into vascular smooth muscle. Furthermore, miR-145 and miR-143 cooperatively targeted a network of transcription factors, including Klf4 (Kruppel-like factor 4), myocardin and Elk-1 (ELK1, member of ETS oncogene family), to promote differentiation and repress proliferation of smooth muscle cells. These findings demonstrate that miR-145 can direct the smooth muscle fate and that miR-145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle cells.