| First Author | Ankawa R | Year | 2021 |
| Journal | Dev Cell | Volume | 56 |
| Issue | 13 | Pages | 1900-1916.e5 |
| PubMed ID | 34197726 | Mgi Jnum | J:313729 |
| Mgi Id | MGI:6730021 | Doi | 10.1016/j.devcel.2021.06.008 |
| Citation | Ankawa R, et al. (2021) Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration. Dev Cell 56(13):1900-1916.e5 |
| abstractText | Stem cells (SCs) play a key role in homeostasis and repair. While many studies have focused on SC self-renewal and differentiation, little is known regarding the molecular mechanism regulating SC elimination and compensation upon loss. Here, we report that Caspase-9 deletion in hair follicle SCs (HFSCs) attenuates the apoptotic cascade, resulting in significant temporal delays. Surprisingly, Casp9-deficient HFSCs accumulate high levels of cleaved caspase-3 and are improperly cleared due to an essential caspase-3/caspase-9 feedforward loop. These SCs are retained in an apoptotic-engaged state, serving as mitogenic signaling centers by continuously releasing Wnt3 and instructing proliferation. Investigating the underlying mechanism, we reveal a caspase-3/Dusp8/p38 module responsible for Wnt3 induction, which operates in both normal and Casp9-deleted HFSCs. Notably, Casp9-deleted mice display accelerated wound repair and de novo hair follicle regeneration. Taken together, we demonstrate that apoptotic cells represent a dynamic SC niche, from which emanating signals drive SC proliferation and tissue regeneration. |
