Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration

Roi Ankawa, Nitzan Goldberger, Yahav Yosefzon, Elle Koren, Marianna Yusupova, Daniel Rosner, Alona Feldman, Shulamit Baror-Sebban, Yosef Buganim, David J. Simon, Marc Tessier-Lavigne, Yaron Fuchs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageAmerican English
Pages (from-to)1900-1916.e5
JournalDevelopmental Cell
Volume56
Issue number13
DOIs
StatePublished - 12 Jul 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • Wnt3
  • apoptosis
  • caspase
  • hair follicle
  • regeneration
  • stem cells
  • wound repair

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