The miR-200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche.
The miR-200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche.
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miR-200家族通过调节上皮干细胞小生境而为外胚层器官发育所需。
DOI：
10.1002/stem.3342
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Amendt BA
中科院分区：
文献类型：
--
作者：
Sweat M;Sweat Y;Yu W;Su D;Leonard RJ;Eliason SL;Amendt BA
小鼠下切牙外胚层器官包含一个上皮干细胞（SC）龛，为持续生长的啮齿动物切牙提供上皮祖细胞。牙科干细胞龛产生了几种细胞类型，我们证明了miR-200家族调节这些细胞的命运。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，我们使用新技术抑制了小鼠胚胎发育中的miR-200家族，导致上皮干细胞龛扩大和细胞分化缺乏。抑制miR-200簇内的单个miR导致差异发育和细胞形态缺陷。miR-200抑制增加了牙上皮干细胞标志物的表达，扩大了干细胞龛并降低了祖细胞分化。RNA测序确定了参与细胞分化和干细胞龛区室化的miR-200调控途径。miR-200家族调节细胞分化和细胞周期进程所需的信号通路。由于自噬和细胞死亡增加，miR-200的抑制降低了下切牙的大小。新的miR-200靶点展示了控制细胞分化和维持干细胞生态位的基因网络和途径。这是第一份证明体内祖细胞增殖和分化如何需要miR-200家族的报告。LaCL干细胞龛不表达调节Sox 2表达的miR-200。离开干细胞龛的祖细胞开始表达miR-200，以促进分化和成熟牙齿发育的细胞命运的特化。因此，miR-200起到分隔干细胞小生境的作用。
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. The LaCL stem cell niche does not express miR‐200, which regulates Sox2 expression. Progenitor cells exiting the stem cell niche start expressing miR‐200 to promote differentiation and the specification of cell fates for mature tooth development. miR‐200 therefore acts to compartmentalize the stem cell niche
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影响因子：
7.2
作者：
McIlwain, David R.;Berger, Thorsten;Mak, Tak W.
通讯作者：
Mak, Tak W.
影响因子：
3
作者：
CHEN, LS;COUWENHOVEN, RI;SNEAD, ML
通讯作者：
SNEAD, ML
影响因子：
16.6
作者：
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通讯作者：
Klein OD
影响因子：
2.7
作者：
Michon, Frederic;Tummers, Mark;Thesleff, Irma
通讯作者：
Thesleff, Irma
影响因子：
7.6
作者：
Cao H;Wang J;Li X;Florez S;Huang Z;Venugopalan SR;Elangovan S;Skobe Z;Margolis HC;Martin JF;Amendt BA
通讯作者：
Amendt BA