PhD Graduate Seminar-Roi Ankawa
23/08/2022 13:00

Apoptoticcells represent a dynamic stem cell niche governing proliferation and tissueregeneration



Stem cells (SCs) play a key role inhomeostasis and repair. While many studies have focused on SC self-renewal anddifferentiation, little is known regarding the molecular mechanism regulatingSC elimination and compensation upon loss. Here, we report that Caspase-9deletion in hair follicle SCs (HFSCs) attenuates the apoptotic cascade,resulting in significant temporal delays. Surprisingly, Casp9-deficient HFSCsaccumulate high levels of cleaved caspase-3 and are improperly cleared due toan essential caspase-3/caspase-9 feedforward loop. These SCs are retained in anapoptotic-engaged state, serving as mitogenic signaling centers by continuouslyreleasing Wnt3 and instructing proliferation. Investigating the underlyingmechanism, we reveal a caspase-3/Dusp8/p38 module responsible for Wnt3induction, which operates in both normal and Casp9-deleted HFSCs. Notably,Casp9-deleted mice display accelerated wound repair and de novo hair follicleregeneration. Taken together, we demonstrate that apoptotic cells represent adynamic SC niche, from which emanating signals drive SC proliferation andtissue regeneration.