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

• Published in: Science advances Vol. 9; no. 43; p. eadg5391
• Main Authors: Rundberg Nilsson, Alexandra J S, Xian, Hongxu, Shalapour, Shabnam, Cammenga, Jörg, Karin, Michael
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 27.10.2023
• Subjects: Animals; Biomedicine and Life Sciences; Cell Biology; Cell Differentiation; Cell Proliferation; Clinical Medicine; Gene Expression Regulation; Hematologi; Hematology; Hematopoietic Stem Cells - metabolism; Humans; Interferon Regulatory Factor-1 - genetics; Interferon Regulatory Factor-1 - metabolism; Klinisk medicin; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Medical and Health Sciences; Medicin och hälsovetenskap; Mice; SciAdv r-articles; Signal Transduction; Stem Cells
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.adg5391

Hematopoietic stem cells (HSCs) are tightly controlled to maintain a balance between blood cell production and self-renewal. While inflammation-related signaling is a critical regulator of HSC activity, the underlying mechanisms and the precise functions of specific factors under steady-state and stress conditions remain incompletely understood. We investigated the role of interferon regulatory factor 1 (IRF1), a transcription factor that is affected by multiple inflammatory stimuli, in HSC regulation. Our findings demonstrate that the loss of IRF1 from mouse HSCs significantly impairs self-renewal, increases stress-induced proliferation, and confers resistance to apoptosis. In addition, given the frequent abnormal expression of in leukemia, we explored the potential of expression level as a stratification marker for human acute myeloid leukemia. We show that -based stratification identifies distinct cancer-related signatures in patient subgroups. These findings establish IRF1 as a pivotal HSC controller and provide previously unknown insights into HSC regulation, with potential implications to IRF1 functions in the context of leukemia.