IRF1 regulates self-renewal and stress-responsiveness to support hematopoietic stem cell maintenance.

ABSTRACT: Inflammatory mediators induce emergency myelopoiesis and cycling of adult hematopoietic stem cells (HSCs) through incompletely understood mechanisms. To suppress the unwanted effects of inflammation and preserve its beneficial outcomes, the mechanisms by which inflammation affects hematopoiesis need to be fully elucidated. Rather than focusing on specific inflammatory stimuli, we here investigated the role of transcription factor Interferon (IFN) regulatory factor 1 (IRF1), which receives input from several inflammatory signaling pathways. We identify IRF1 as a master HSC regulator. IRF1 loss impairs HSC self-renewal, increases stress-induced cell cycle activation, and confers apoptosis resistance. Transcriptomic analysis revealed an aged, inflammatory signature devoid of IFN signaling wit

SUBMITTER: Rundberg Nilsson A 

PROVIDER: S-EPMC9900858 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature