miR-145 and miR-143 Regulate Smooth Muscle Cell Fate Decisions

By Kimberly R. Cordes, N. Sheehy, Mark P. White, E. Berry, S. Morton, Alecia N. Muth, Ting-Hein Lee, J. Miano, Kathryn N. Ivey, Deepak Srivastava. Nature, 2009

896 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/03ee030ea00b09cc608eca7d187c74056f595504

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In Cancer Research

1. E. Olson
2. E. Small
3. J. Richardson
4. C. Burge
5. David P. Bartel
6. Phillip A. Sharp
7. Eva van Rooij
8. Joshua T. Mendell

In Molecular Biology

1. E. Olson
2. J. Richardson
3. R. Bassel-Duby
4. E. Small
5. X. Qi
6. L. Sutherland
7. Quan Zou
8. C. Burge

Citations in the corpus

• Biological functions of microRNAs: a review (2011, background): “Cordes et al. [ 9 ] demonstrated that miR-145 can direct smooth muscle fate, and that miR- 145 and miR-143 function to regulate the quiescent versus proliferative phenotype of smooth muscle”
• Pervasive roles of microRNAs in cardiovascular biology (2011, background): “miR-145 has been reported to be necessary and sufficient for SMC differentiation in vitro”
• Pathophysiology of Atherosclerosis (2022, background): “The discovery that the expression of miR-143/145 is critical for maintaining the contractile phenotype of VSMCs [305,306] highlighted the role of the bicistrionic unit encoding for miR-143 and miR-145 in the regulation of smooth muscle physiology [306,307].”
• MicroRNAs miR-143 and miR-145 modulate cytoskeletal dynamics and responsiveness of smooth muscle cells to injury. (2009, background): “Recent studies have revealed key roles for microRNAs (miRNAs) in the control of cardiac and skeletal muscle development and remodeling in response to injury (van Rooij and Olson 2007; Condorelli and Dimmeler 2008; Chen et al. 2009; Cordes and Srivastava 2009).”
• Braveheart, a long non-coding RNA required for cardiovascular lineage commitment (2013, background): “Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes.”