生物
Notch信号通路
细胞生物学
潘尼斯电池
干细胞
祖细胞
地穴
再生(生物学)
细胞分化
类有机物
信号转导
遗传学
内分泌学
基因
小肠
作者
Natacha Bohin,Theresa M. Keeley,Alexis J. Carulli,Emily M. Walker,Elizabeth Carlson,Jie Gao,Iannis Aifantis,Christian W. Siebel,Michael W. Rajala,Martin G. Myers,Jennifer Jones,Constance D. Brindley,Peter J. Dempsey,Linda C. Samuelson
标识
DOI:10.1016/j.stemcr.2020.05.010
摘要
Intestinal crypts have great capacity for repair and regeneration after intestinal stem cell (ISC) injury. Here, we define the cellular remodeling process resulting from ISC niche interruption by transient Notch pathway inhibition in adult mice. Although ISCs were retained, lineage tracing demonstrated a marked reduction in ISC function after Notch disruption. Surprisingly, Notch ligand-expressing Paneth cells were rapidly lost by apoptotic cell death. The ISC-Paneth cell changes were followed by a regenerative response, characterized by expansion of cells expressing Notch ligands Dll1 and Dll4, enhanced Notch signaling, and a proliferative surge. Lineage tracing and organoid studies showed that Dll1-expressing cells were activated to function as multipotential progenitors, generating both absorptive and secretory cells and replenishing the vacant Paneth cell pool. Our analysis uncovered a dynamic, multicellular remodeling response to acute Notch inhibition to repair the niche and restore homeostasis. Notably, this crypt regenerative response did not require ISC loss.
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