| First Author | Rundberg Nilsson AJS | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 43 | Pages | eadg5391 |
| PubMed ID | 37889967 | Mgi Jnum | J:342211 |
| Mgi Id | MGI:7546439 | Doi | 10.1126/sciadv.adg5391 |
| Citation | Rundberg Nilsson AJS, et al. (2023) IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance. Sci Adv 9(43):eadg5391 |
| abstractText | 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 IRF1 in leukemia, we explored the potential of IRF1 expression level as a stratification marker for human acute myeloid leukemia. We show that IRF1-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. |
