BECN1 modulates hematopoietic stem cells by targeting Caspase-3-GSDME-mediated pyroptosis

Xiuxiu Yang; Liang Ge; Jianwei Wang

doi:10.1097/BS9.0000000000000051

BECN1 modulates hematopoietic stem cells by targeting Caspase-3-GSDME-mediated pyroptosis

Blood Sci. 2020 Jul 25;2(3):89-99. doi: 10.1097/BS9.0000000000000051. eCollection 2020 Jul.

Authors

Xiuxiu Yang¹, Liang Ge², Jianwei Wang^{1

3}

Affiliations

¹ School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
² School of Life Sciences, Tsinghua University, Beijing 100084, China.
³ Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing 100084, China.

Abstract

Hematopoietic stem cells (HSCs) maintain the blood system throughout the lifespan. However, the molecular mechanism maintaining HSC character remains not fully understood. In this study, we observed that the targeted deletion of Becn1 disrupts the blood system and impairs the reconstitution capacity of HSCs. Interestingly, Becn1 deletion did not lead to dysfunction of autophagy in HSCs, indicating a non-classical role of BECN1 in regulating HSCs function. While we observed the increase of Caspase-3-GSDME-mediated pyroptosis in Becn1 deficient hematopoietic stem and progenitor cells. Forced expression of the full-length GSDME compromises the function of HSCs. In brief, we identified a novel role of Becn1 in modulating HSCs by regulating pyroptosis, but not through autophagy. This study provides a new link between BECN1-Caspase-3-GSDME signaling and HSC maintenance.

Keywords: Autophagy; Becn1; Cell death; Hematopoietic stem cell; Pyroptosis.