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Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic resilience to cytotoxic stress

Zhang, Qinyu LU orcid ; Rydström, Anna LU ; Hidalgo, Isabel LU orcid ; Cammenga, Jörg LU and Rundberg Nilsson, Alexandra LU orcid (2025) In International Journal of Biochemistry and Cell Biology 186.
Abstract

Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system's resilience to subsequent... (More)

Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system's resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II- HSCs - a subset characterized by high self-renewal potential and hypersensitivity to irradiation-induced ROS production. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by substantially reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
International Journal of Biochemistry and Cell Biology
volume
186
article number
106814
publisher
Elsevier
external identifiers
  • scopus:105007356471
  • pmid:40473015
ISSN
1878-5875
DOI
10.1016/j.biocel.2025.106814
language
English
LU publication?
yes
additional info
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
id
4857b91e-aec4-4381-b02f-349c93dfbc08
date added to LUP
2025-07-14 16:31:02
date last changed
2025-07-16 03:28:48
@article{4857b91e-aec4-4381-b02f-349c93dfbc08,
  abstract     = {{<p>Irradiation and 5-fluorouracil (5-FU) are widely utilized tools in hematopoietic research to generate myeloablation and assess blood recovery dynamics. A comprehensive understanding of their effects on the hematopoietic system is essential for optimizing therapeutic strategies, refining experimental models to modulate hematotoxicity, and interpreting research outcomes. Despite their widespread application, the long-term hematopoietic impacts of irradiation and 5-FU, particularly on hematopoietic stem cells (HSCs), remain incompletely characterized. In this study, we therefore examined the long-term effects of 2 Gy medium-dose ionizing radiation (MDIR) and 150 mg/kg 5-FU on HSCs and the hematopoietic system's resilience to subsequent cytotoxic stress in mice. Our findings demonstrate that MDIR, but not 5-FU, induces sustained impairments in HSC function and results in the selective depletion of MHC class II- HSCs - a subset characterized by high self-renewal potential and hypersensitivity to irradiation-induced ROS production. Furthermore, MDIR significantly compromised hematopoietic recovery following a subsequent 5-FU challenge, as evidenced by substantially reduced platelet and red blood cell (RBC) counts during the critical recovery phase. These findings highlight the distinct and persistent impacts of MDIR and 5-FU on HSCs and hematopoietic function, revealing crucial differences in their mechanisms of action and long-term consequences on the hematopoietic system.</p>}},
  author       = {{Zhang, Qinyu and Rydström, Anna and Hidalgo, Isabel and Cammenga, Jörg and Rundberg Nilsson, Alexandra}},
  issn         = {{1878-5875}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{International Journal of Biochemistry and Cell Biology}},
  title        = {{Medium-dose irradiation impairs long-term hematopoietic stem cell functionality and hematopoietic resilience to cytotoxic stress}},
  url          = {{http://dx.doi.org/10.1016/j.biocel.2025.106814}},
  doi          = {{10.1016/j.biocel.2025.106814}},
  volume       = {{186}},
  year         = {{2025}},
}