生物
利基
间充质干细胞
Wnt信号通路
细胞生物学
骨形态发生蛋白
形态发生
干细胞
细胞分化
地穴
信号转导
生态学
内分泌学
遗传学
基因
作者
Neil McCarthy,Guodong Tie,Shariq Madha,Ruiyang He,Judith Kraiczy,Adrianna Maglieri,Ramesh A. Shivdasani
标识
DOI:10.1016/j.devcel.2023.02.012
摘要
Summary
Wnt and Rspondin (RSPO) signaling drives proliferation, and bone morphogenetic protein inhibitors (BMPi) impede differentiation, of intestinal stem cells (ISCs). Here, we identify the mouse ISC niche as a complex, multi-layered structure that encompasses distinct mesenchymal and smooth muscle populations. In young and adult mice, diverse sub-cryptal cells provide redundant ISC-supportive factors; few of these are restricted to single cell types. Niche functions refine during postnatal crypt morphogenesis, in part to oppose the dense aggregation of differentiation-promoting BMP+ sub-epithelial myofibroblasts at crypt-villus junctions. Muscularis mucosae, a specialized muscle layer, first appears during this period and supplements neighboring RSPO and BMPi sources. Components of this developing niche are conserved in human fetuses. The in vivo ablation of mouse postnatal smooth muscle increases BMP signaling activity, potently limiting a pre-weaning burst of crypt fission. Thus, distinct and progressively specialized mesenchymal cells together create the milieu that is required to propagate crypts during rapid organ growth and to sustain adult ISCs.
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