Hwang Supyong, Park Seul-Ki, Lee Ha Yeon, Kim Seong Who, Lee Jung Shin, Choi Eun Kyung, You Dalsan, Kim Choung-Soo, Suh Nayoung
Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea; Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
FEBS Lett. 2014 Aug 25;588(17):2957-63. doi: 10.1016/j.febslet.2014.05.048. Epub 2014 Jun 10.
Human mesenchymal stem cells (hMSCs) have self-renewal and differentiation capabilities but the regulatory mechanisms of MSC fate determination remain poorly understood. Here, we aimed to identify microRNAs enriched in hMSCs that modulate differentiation commitments. Microarray analysis revealed that miR-140-5p is commonly enriched in undifferentiated hMSCs from various tissue sources. Moreover, bioinformatic analysis and luciferase reporter assay validated that miR-140-5p directly represses bone morphogenic protein 2 (BMP2). Furthermore, blocking miR-140-5p in hMSCs increased the expression of BMP signaling components and critical regulators of osteogenic differentiation. We propose that miR-140-5p functionally inhibits osteogenic lineage commitment in undifferentiated hMSCs.
人骨髓间充质干细胞(hMSCs)具有自我更新和分化能力,但间充质干细胞命运决定的调控机制仍知之甚少。在这里,我们旨在鉴定在hMSCs中富集的、调节分化定向的微小RNA。微阵列分析显示,miR-140-5p在来自各种组织来源的未分化hMSCs中普遍富集。此外,生物信息学分析和荧光素酶报告基因检测证实,miR-140-5p直接抑制骨形态发生蛋白2(BMP2)。此外,在hMSCs中阻断miR-140-5p可增加BMP信号成分和成骨分化关键调节因子的表达。我们提出,miR-140-5p在功能上抑制未分化hMSCs中的成骨谱系定向。