Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
The Craniofacial Anomalies Research Center, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Stem Cells. 2021 Jun;39(6):761-775. doi: 10.1002/stem.3342. Epub 2021 Feb 13.
The murine lower incisor ectodermal organ contains a single epithelial stem cell (SC) niche that provides epithelial progenitor cells to the continuously growing rodent incisor. The dental stem cell niche gives rise to several cell types and we demonstrate that the miR-200 family regulates these cell fates. The miR-200 family is highly enriched in the differentiated dental epithelium and absent in the stem cell niche. In this study, we inhibited the miR-200 family in developing murine embryos using new technology, resulting in an expanded epithelial stem cell niche and lack of cell differentiation. Inhibition of individual miRs within the miR-200 cluster resulted in differential developmental and cell morphology defects. miR-200 inhibition increased the expression of dental epithelial stem cell markers, expanded the stem cell niche and decreased progenitor cell differentiation. RNA-seq. identified miR-200 regulatory pathways involved in cell differentiation and compartmentalization of the stem cell niche. The miR-200 family regulates signaling pathways required for cell differentiation and cell cycle progression. The inhibition of miR-200 decreased the size of the lower incisor due to increased autophagy and cell death. New miR-200 targets demonstrate gene networks and pathways controlling cell differentiation and maintenance of the stem cell niche. This is the first report demonstrating how the miR-200 family is required for in vivo progenitor cell proliferation and differentiation.
小鼠下切牙外胚层器官包含一个单一的上皮干细胞 (SC) 龛，为不断生长的啮齿动物切牙提供上皮祖细胞。牙干细胞龛产生多种细胞类型，我们证明 miR-200 家族调节这些细胞命运。miR-200 家族在分化的牙上皮中高度富集，而在干细胞龛中不存在。在这项研究中，我们使用新技术在发育中的小鼠胚胎中抑制 miR-200 家族，导致上皮干细胞龛扩大和缺乏细胞分化。miR-200 簇中单个 miR 的抑制导致发育和细胞形态缺陷的差异。miR-200 抑制增加了牙上皮干细胞标志物的表达，扩大了干细胞龛并减少了祖细胞分化。RNA-seq. 确定了 miR-200 调节与细胞分化和干细胞龛区室化相关的信号通路。miR-200 家族调节细胞分化和细胞周期进程所需的信号通路。miR-200 的抑制由于自噬和细胞死亡增加，导致下切牙变小。新的 miR-200 靶标表明控制细胞分化和维持干细胞龛的基因网络和途径。这是第一个证明 miR-200 家族如何在体内祖细胞增殖和分化中发挥作用的报告。
