Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Nilsson, Alexandra Rundberg LU ; Xian, Hongxu ; Shalapour, Shabnam ; Cammenga, Jörg LU and Karin, Michael (2023)
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,... (More)
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 with reduced megakaryocytic/erythroid priming and antigen presentation in IRF1-deficient HSCs. Finally, we conducted IRF1-based AML patient stratification to identify groups with distinct proliferative, survival and differentiation features, overlapping with our murine HSC results. Our findings position IRF1 as a pivotal regulator of HSC preservation and stress-induced responses.Competing Interest StatementThe authors have declared no competing interest. (Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Working paper/Preprint
publication status
published
subject
publisher
bioRxiv
external identifiers
  • pmid:36747722
DOI
10.1101/2023.01.24.525321
language
English
LU publication?
yes
id
86c97010-d205-45ce-b470-6dfcac1e9008
date added to LUP
2023-05-22 11:33:07
date last changed
2023-05-23 03:00:12
@misc{86c97010-d205-45ce-b470-6dfcac1e9008,
  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 with reduced megakaryocytic/erythroid priming and antigen presentation in IRF1-deficient HSCs. Finally, we conducted IRF1-based AML patient stratification to identify groups with distinct proliferative, survival and differentiation features, overlapping with our murine HSC results. Our findings position IRF1 as a pivotal regulator of HSC preservation and stress-induced responses.Competing Interest StatementThe authors have declared no competing interest.}},
  author       = {{Nilsson, Alexandra Rundberg and Xian, Hongxu and Shalapour, Shabnam and Cammenga, Jörg and Karin, Michael}},
  language     = {{eng}},
  month        = {{01}},
  note         = {{Preprint}},
  publisher    = {{bioRxiv}},
  title        = {{IRF1 regulates self-renewal and stress-responsiveness to support hematopoietic stem cell maintenance}},
  url          = {{http://dx.doi.org/10.1101/2023.01.24.525321}},
  doi          = {{10.1101/2023.01.24.525321}},
  year         = {{2023}},
}