Progenitor function in self-renewing human epidermis is maintained by the exosome.

Progenitor function in self-renewing human epidermis is maintained by the exosome.
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DOI:
10.1016/j.stem.2012.04.022
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发表时间:
2012-07-06
期刊:
影响因子:
23.9
通讯作者:
Sen, George L.
Sen, George L.
中科院分区:
医学1区
文献类型:
--
作者:
Mistry, Devendra S.;Chen, Yifang;Sen, George L.

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干细胞和祖细胞通过调节增殖和分化之间的平衡来维持它们所居住的组织的终生。这是如何完成的尚不清楚。在这里,我们报告人类外泌体维持祖细胞功能。外泌体的几个亚基的表达被发现在表皮祖细胞中富集,这是保留增殖能力和防止过早分化所必需的。 PM/Scl-75(也称为 EXOSC9)(外泌体复合物的关键亚基)的缺失会导致祖细胞区室细胞的丢失、过早分化和表皮组织的丢失。 EXOSC9 通过 mRNA 降解将表皮分化所需的转录因子 GRHL3 的转录水平维持在低水平,从而促进自我更新并防止过早分化。这些数据表明,哺乳动物组织中祖细胞的维持需要通过 mRNA 降解来控制分化特异性转录因子。
Stem and progenitor cells maintain the tissue they reside in for life by regulating the balance between proliferation and differentiation. How this is done is not well understood. Here, we report that the human exosome maintains progenitor cell function. The expression of several subunits of the exosome were found to be enriched in epidermal progenitor cells, which were required to retain proliferative capacity and to prevent premature differentiation. Loss of PM/Scl-75 also known as EXOSC9, a key subunit of the exosome complex, resulted in loss of cells from the progenitor cell compartment, premature differentiation, and loss of epidermal tissue. EXOSC9 promotes self-renewal and prevents premature differentiation by maintaining transcript levels of a transcription factor necessary for epidermal differentiation, GRHL3, at low levels through mRNA degradation. These data demonstrate that control of differentiation specific transcription factors through mRNA degradation is required for progenitor cell maintenance in mammalian tissue.
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