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

Kimberly R. Cordes, Neil T. Sheehy, Mark P. White, Emily C. Berry, Sarah U. Morton, Alecia N. Muth, Ting Hein Lee, Joseph M. Miano, Kathryn N. Ivey, Deepak Srivastava

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)705-710
Number of pages6
JournalNature
Volume460
Issue number7256
DOIs
StatePublished - Aug 6 2009

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Smooth Muscle Myocytes
Multipotent Stem Cells
Neural Stem Cells
Neural Crest
MicroRNAs
Vascular Smooth Muscle
Transcription Factors
Serum Response Factor
Oncogenes
Smooth Muscle
Cell Plasticity
Down-Regulation
Fibroblasts
Phenotype
myocardin

ASJC Scopus subject areas

  • General

Cite this

Cordes, K. R., Sheehy, N. T., White, M. P., Berry, E. C., Morton, S. U., Muth, A. N., ... Srivastava, D. (2009). MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature, 460(7256), 705-710. https://doi.org/10.1038/nature08195

MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity. / Cordes, Kimberly R.; Sheehy, Neil T.; White, Mark P.; Berry, Emily C.; Morton, Sarah U.; Muth, Alecia N.; Lee, Ting Hein; Miano, Joseph M.; Ivey, Kathryn N.; Srivastava, Deepak.

In: Nature, Vol. 460, No. 7256, 06.08.2009, p. 705-710.

Research output: Contribution to journalArticle

Cordes, KR, Sheehy, NT, White, MP, Berry, EC, Morton, SU, Muth, AN, Lee, TH, Miano, JM, Ivey, KN & Srivastava, D 2009, 'MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity', Nature, vol. 460, no. 7256, pp. 705-710. https://doi.org/10.1038/nature08195
Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN et al. MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009 Aug 6;460(7256):705-710. https://doi.org/10.1038/nature08195
Cordes, Kimberly R. ; Sheehy, Neil T. ; White, Mark P. ; Berry, Emily C. ; Morton, Sarah U. ; Muth, Alecia N. ; Lee, Ting Hein ; Miano, Joseph M. ; Ivey, Kathryn N. ; Srivastava, Deepak. / MiR-145 and miR-143 regulate smooth muscle cell fate and plasticity. In: Nature. 2009 ; Vol. 460, No. 7256. pp. 705-710.
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