Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.

ABSTRACT: Receptor tyrosine kinases (RTKs) control stem cell maintenance vs. differentiation decisions. Casitas B-lineage lymphoma (CBL) family ubiquitin ligases are negative regulators of RTKs, but their stem cell regulatory roles remain unclear. Here, we show that Lgr5+ intestinal stem cell (ISC)-specific inducible Cbl-knockout (KO) on a Cblb null mouse background (iDKO) induced rapid loss of the Lgr5 ^Hi ISCs with transient expansion of the Lgr5 ^Lo transit-amplifying population. LacZ-based lineage tracing revealed increased ISC commitment toward enterocyte and goblet cell fate at the expense of Paneth cells. Functionally, Cbl/Cblb iDKO impaired the recovery from radiation-induced intestinal epithelial injury. In vitro, Cbl/Cblb

SUBMITTER: Zutshi N 

PROVIDER: S-EPMC11225835 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature