IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance
(2023) In Science Advances 9(43).- Abstract
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... (More)
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.
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- author
- Rundberg Nilsson, Alexandra J.S. LU ; Xian, Hongxu ; Shalapour, Shabnam ; Cammenga, Jörg LU and Karin, Michael
- organization
- publishing date
- 2023-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science Advances
- volume
- 9
- issue
- 43
- article number
- eadg5391
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- pmid:37889967
- scopus:85175279379
- ISSN
- 2375-2548
- DOI
- 10.1126/sciadv.adg5391
- language
- English
- LU publication?
- yes
- id
- 892b48b6-8712-4c20-9372-2a671a18b5a1
- date added to LUP
- 2023-12-11 14:41:25
- date last changed
- 2024-04-24 08:08:47
@article{892b48b6-8712-4c20-9372-2a671a18b5a1, abstract = {{<p>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.</p>}}, author = {{Rundberg Nilsson, Alexandra J.S. and Xian, Hongxu and Shalapour, Shabnam and Cammenga, Jörg and Karin, Michael}}, issn = {{2375-2548}}, language = {{eng}}, number = {{43}}, publisher = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science Advances}}, title = {{IRF1 regulates self-renewal and stress responsiveness to support hematopoietic stem cell maintenance}}, url = {{http://dx.doi.org/10.1126/sciadv.adg5391}}, doi = {{10.1126/sciadv.adg5391}}, volume = {{9}}, year = {{2023}}, }