GSDME maintains hematopoietic stem cells by balancing pyroptosis and apoptosis

Abstract

Abstract. GSDME contains a pore-forming domain at its N-terminal region to execute pyroptosis. Our previous study has reported that forced expression of Gsdme impairs the reconstitution capacity of hematopoietic stem cells (HSCs). While, how GSDME-mediated pyroptosis regulates HSCs remains unknown. Here, we show that hematopoietic stem and progenitor cells are capable to undergo pyroptosis in response to cisplatin treatment and GSDME is one of the genes mediating such process. Gsdme−/− mice revealed no difference in the steady state of blood system while Gsdme−/− HSCs exhibited compromised reconstitution capacity due to increased apoptosis. Briefly, this study reveals that GSDME modulates HSC function by coordinating pyroptosis and apoptosis.