Faculty Opinions recommendation of Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells [dataset]

Avri Ben-Ze'ev
2020 Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature   unpublished
Ablation of LGR5 + intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment. Different intestinal crypt populations dedifferentiate to provide new ISCs, but the transcriptional and signaling trajectories that guide this process are unclear, and a large body of work suggests that quiescent 'reserve' ISCs contribute toward regeneration. By timing the interval between LGR5 + lineage tracing and lethal injury, we show that ISC regeneration is explained nearly
more » ... ly by dedifferentiation, with contributions from absorptive and secretory progenitors. The ISC-restricted transcription factor ASCL2 confers measurable competitive advantage to resting ISCs and is essential to restore the ISC compartment. Regenerating cells reexpress Ascl2 days before Lgr5, and scRNAseq analyses reveal transcriptional paths underlying dedifferentiation. ASCL2 target genes include the Interleukin11 (IL11) receptor Il11ra1, and recombinant IL11 enhances crypt cell regenerative potential. These findings reveal cell *
doi:10.3410/f.737406584.793577718 fatcat:dguicoj4cngi5ksfe25wx4yynm