miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.
miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.
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DOI：
10.1038/nature08195
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发表时间：
2009-08-06
期刊：
影响因子：
64.8
通讯作者：
Srivastava D
中科院分区：
文献类型：
--
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
microRNA是无数细胞事件的调节剂，但是单个microRNA可以有效地将多功能细胞区分为特定的谱系，或者将细胞直接重编程为替代细胞命运，我们在这里表明mir-145和mir-- mir-- 143在多能的心脏祖细胞中共转录，然后再将其定位于平滑肌细胞，包括神经crest干细胞衍生的血管平滑肌细胞。 miR-145和miR-143是血清反应因子，心肌蛋白和NKX2.5的直接转录靶标，在受伤或动脉粥样硬化的血管中被下调，这些血管含有增殖，较少的平滑肌细胞是肌肉素诱导的。成年成纤维细胞进入平滑肌细胞，足以诱导多能神经rest干细胞分化为血管平滑肌。此外，miR-145和miR-143的靶向转录因子网络，包括KLF4，肌电蛋白和ELK-1，以促进分化并反映平滑肌细胞的增殖。 MiR-145和miR-143的功能可以调节平滑肌细胞的静止与增殖表型。
microRNAs are regulators of myriad cellular events, but evidence for a single microRNA that can efficiently differentiate multipotent cells into a specific lineage or regulate direct reprogramming of cells into an alternate cell fate has been elusive. Here, we show that miR-145 and miR-143 are co-transcribed in multipotent 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, 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, myocardin, and Elk-1 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.
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DOI：
10.1073/pnas.0509535102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Kwon, C;Han, Z;Srivastava, D
通讯作者：
Srivastava, D
影响因子：
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影响因子：
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影响因子：
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作者：
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影响因子：
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