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Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery

Rundberg Nilsson, Alexandra LU ; Hidalgo, Isabel LU orcid ; Bryder, David LU and Pronk, Cornelis Jan (2023) In iScience 26(4).
Abstract

While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-renewal capacity of hematopoietic stem cells (HSCs), but its long-term effect on HSCs remains unclear. Here, we demonstrate that in vivo TNF administration results in a transient exit of HSCs from quiescence, which coincides with a compromised repopulation capacity. These functional changes are; however, fully reversible even following... (More)

While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-renewal capacity of hematopoietic stem cells (HSCs), but its long-term effect on HSCs remains unclear. Here, we demonstrate that in vivo TNF administration results in a transient exit of HSCs from quiescence, which coincides with a compromised repopulation capacity. These functional changes are; however, fully reversible even following prolonged/chronic transient exposure to TNF. Notably, antagonizing TNF signaling in transplantation recipients enhances donor HSC reconstitution. Our findings provide molecular and functional insight into HSC regulation, with implications for both acute and chronic inflammatory conditions.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biological sciences, Cell biology, Molecular biology, Stem cells research
in
iScience
volume
26
issue
4
article number
106341
publisher
Elsevier
external identifiers
  • scopus:85150262885
  • pmid:36968066
ISSN
2589-0042
DOI
10.1016/j.isci.2023.106341
language
English
LU publication?
yes
id
0888aa20-b0c2-49db-8884-2e4a4d3a3e09
date added to LUP
2023-04-24 12:18:29
date last changed
2024-09-21 11:13:27
@article{0888aa20-b0c2-49db-8884-2e4a4d3a3e09,
  abstract     = {{<p>While tumor necrosis factor (TNF) is a critical mediator of appropriate immune response and tissue repair, its misregulation is linked to cancer, autoimmunity, bone marrow failure, and aging. Understanding the context-dependent roles of TNF is essential for elucidating normal and pathogenic conditions and to guide clinical therapy advancements. Prior studies suggested that TNF restricts the self-renewal capacity of hematopoietic stem cells (HSCs), but its long-term effect on HSCs remains unclear. Here, we demonstrate that in vivo TNF administration results in a transient exit of HSCs from quiescence, which coincides with a compromised repopulation capacity. These functional changes are; however, fully reversible even following prolonged/chronic transient exposure to TNF. Notably, antagonizing TNF signaling in transplantation recipients enhances donor HSC reconstitution. Our findings provide molecular and functional insight into HSC regulation, with implications for both acute and chronic inflammatory conditions.</p>}},
  author       = {{Rundberg Nilsson, Alexandra and Hidalgo, Isabel and Bryder, David and Pronk, Cornelis Jan}},
  issn         = {{2589-0042}},
  keywords     = {{Biological sciences; Cell biology; Molecular biology; Stem cells research}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Temporal dynamics of TNF-mediated changes in hematopoietic stem cell function and recovery}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2023.106341}},
  doi          = {{10.1016/j.isci.2023.106341}},
  volume       = {{26}},
  year         = {{2023}},
}