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Rapid Crypt Cell Remodeling Regenerates the Intestinal Stem Cell Niche after Notch Inhibition.

Abstract：

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Bohin N,Keeley TM,Carulli AJ,Walker EM,Carlson EA,Gao J,Aifantis I,Siebel CW,Rajala MW,Myers MG Jr,Jones JC,Brindley CD,Dempsey PJ,Samuelson LC

doi

10.1016/j.stemcr.2020.05.010

subject

Has Abstract

pub_date

2020-07-14 00:00:00

pages

156-170

issue

1

issn

2213-6711

pii

S2213-6711(20)30182-X

journal_volume

15

pub_type

杂志文章

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