AI Article Synopsis
- - Intestinal stem cells (ISCs) can repair themselves after injury, but temporarily blocking the Notch signaling pathway reduces their function despite retaining ISCs.
- - The loss of Notch ligand-expressing Paneth cells occurs through cell death, which triggers a regenerative response where cells expressing Dll1 and Dll4 expand and enhance Notch signaling.
- - Dll1-expressing cells then take on a multipotential role, creating both absorptive and secretory cells to replace lost Paneth cells, illustrating a complex repair mechanism that doesn't rely on losing ISCs.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363878 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2020.05.010 | DOI Listing |
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