Embryogenic stem cell-derived intestinal crypt fission directs de novo crypt genesis
Embryogenic stem cell-derived intestinal crypt fission directs de novo crypt genesis
复制标题
胚胎干细胞衍生的肠隐窝分裂指导隐窝从头发生
DOI：
10.1016/j.celrep.2022.111796
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发表时间：
2022
期刊：
影响因子：
8.8
通讯作者：
Yang Wei-Jun
中科院分区：
文献类型：
--
作者：
Huang Xue-Ting;Li Ting;Li Tong;Xing Sheng;Tian Jin-Ze;Ding Yan-Fu;Cai Sun-Li;Yang Yao-Shun;Wood Christopher;Yang Jin-Shu;Yang Wei-Jun
肠道上皮细胞的补充是通过持续分裂驻留在隐窝内的肠道干细胞(ISCs)来实现的。然而，能够在受损后重新补充以及随后整个隐窝丢失的细胞类型(S)在很大程度上仍不清楚。利用SET结构域包含蛋白4(SetD4)，我们在小鼠肠道中鉴定出一个具有储备干细胞特征的小种群。辐射损伤后，表达Setd4的细胞在辐射后存活，然后激活产生表达Sca-1的细胞类型，以恢复上皮壁和再生新隐窝的分裂。Setd4+细胞被证实起源于胎儿早期，随后有助于胚胎肠道的发育和出生后隐窝的建立。因此，Setd4+细胞既是肠道的始发者，也是关键的再生者。
Intestinal epithelial replenishment is fueled by continuously dividing intestinal stem cells (ISCs) resident at the crypt niche. However, the cell type(s) enabling replenishment upon damage and subsequent loss of whole crypts remain largely unclear. Using Set domain-containing protein 4 (Setd4), we identify a small population with reserve stem cell characteristics in the mouse intestine. Upon irradiation-induced injury, Setd4-expressing (Setd4+) cells survive radiation exposure and then activate to produce Sca-1-expressing cell types to restore the epithelial wall and regenerate cryptsde novovia crypt fission. Setd4+cells are confirmed to originate from the early fetal period, subsequently contributing to the development of embryonic gut and the establishment of postnatal crypts. Setd4+cells are therefore represented as both originators and key regenerators of the intestine.