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Main Authors: Chao Zhang, Weiwei Yi, Zhehua Shao, Bingpeng Yao, Guoxiong Tian, Fei Li, Xufei Du, Yangmingzi Hu, Yanqi Guo, Tao Wu, Wen Li, Zhihua Chen, Zhenyu Ju, Songmin Ying
Format: Artículo Open Access
Published: Wiley 2025
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Online Access:https://onlinelibrary.wiley.com/doi/10.1111/all.70021
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author Chao Zhang
Weiwei Yi
Zhehua Shao
Bingpeng Yao
Guoxiong Tian
Fei Li
Xufei Du
Yangmingzi Hu
Yanqi Guo
Tao Wu
Wen Li
Zhihua Chen
Zhenyu Ju
Songmin Ying
author_facet Chao Zhang
Weiwei Yi
Zhehua Shao
Bingpeng Yao
Guoxiong Tian
Fei Li
Xufei Du
Yangmingzi Hu
Yanqi Guo
Tao Wu
Wen Li
Zhihua Chen
Zhenyu Ju
Songmin Ying
Chao Zhang
Weiwei Yi
Zhehua Shao
Bingpeng Yao
Guoxiong Tian
Fei Li
Xufei Du
Yangmingzi Hu
Yanqi Guo
Tao Wu
Wen Li
Zhihua Chen
Zhenyu Ju
Songmin Ying
collection Wiley Open Access
contents Physiological Level of Eosinophils Is Essential for the Regeneration and Homeostasis of Murine Hematopoietic Stem Cells Chao Zhang Weiwei Yi Zhehua Shao Bingpeng Yao Guoxiong Tian Fei Li Xufei Du Yangmingzi Hu Yanqi Guo Tao Wu Wen Li Zhihua Chen Zhenyu Ju Songmin Ying Allergy ABSTRACT Background Eosinophils play a crucial role in host defense and immunity, yet their regulatory functions within the hematopoietic homeostasis remain poorly understood. Our prior investigations revealed that pathologically elevated eosinophil levels in asthma not only disrupt bone marrow hematopoietic stem cell (HSC) quiescence but also establish a self‐reinforcing cycle of eosinophil lineage commitment. Here, we further investigate the critical role of physiologically steady‐state levels of eosinophils in maintaining HSC functions. Methods Using eosinophil lineage‐specific null (Eos‐null) mice, we established models of chemotherapy‐induced HSC regeneration and competitive bone marrow transplantation (cBMT) assay to evaluate the impact of eosinophil depletion on HSC regeneration and function. In vitro colony forming assay assessed HSC reconstitute capability, while bone marrow chimeric mice were established with wild‐type (WT) and eosinophil‐related transgenic mice to further elucidate the role of physiological levels of eosinophils. RNA‐seq and cytokine array analyses were utilized to investigate the potential protective mechanisms of eosinophils. Results Compared to WT controls, Eos‐null mice exhibited significantly impaired HSC regeneration, characterized by a diminished response to 5‐fluorouracil (5‐FU) and carboplatin treatment. Both long‐term HSCs (LT‐HSCs) and lineage − Sca‐1 + c‐Kit + (LSK) demonstrated compromised reconstitution capacity in vivo and in vitro. HSCs from Eos‐null mice demonstrated elevated apoptosis under 5‐FU treatment, potentially due to the absence of eosinophil‐derived protective factors. Conversely, both chimeric mice and eosinophil incorporation within bone marrow transplantation systems significantly disrupted HSC homeostasis and function. Conclusion Physiological eosinophil level is essential for maintaining HSC regeneration, reconstitution capacity, and homeostasis. 10.1111/all.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1111/all.70021
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institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2025
publisher Wiley
record_format wiley_oa
spellingShingle Physiological Level of Eosinophils Is Essential for the Regeneration and Homeostasis of Murine Hematopoietic Stem Cells
Chao Zhang
Weiwei Yi
Zhehua Shao
Bingpeng Yao
Guoxiong Tian
Fei Li
Xufei Du
Yangmingzi Hu
Yanqi Guo
Tao Wu
Wen Li
Zhihua Chen
Zhenyu Ju
Songmin Ying
Allergy
Physiological Level of Eosinophils Is Essential for the Regeneration and Homeostasis of Murine Hematopoietic Stem Cells Chao Zhang Weiwei Yi Zhehua Shao Bingpeng Yao Guoxiong Tian Fei Li Xufei Du Yangmingzi Hu Yanqi Guo Tao Wu Wen Li Zhihua Chen Zhenyu Ju Songmin Ying Allergy ABSTRACT Background Eosinophils play a crucial role in host defense and immunity, yet their regulatory functions within the hematopoietic homeostasis remain poorly understood. Our prior investigations revealed that pathologically elevated eosinophil levels in asthma not only disrupt bone marrow hematopoietic stem cell (HSC) quiescence but also establish a self‐reinforcing cycle of eosinophil lineage commitment. Here, we further investigate the critical role of physiologically steady‐state levels of eosinophils in maintaining HSC functions. Methods Using eosinophil lineage‐specific null (Eos‐null) mice, we established models of chemotherapy‐induced HSC regeneration and competitive bone marrow transplantation (cBMT) assay to evaluate the impact of eosinophil depletion on HSC regeneration and function. In vitro colony forming assay assessed HSC reconstitute capability, while bone marrow chimeric mice were established with wild‐type (WT) and eosinophil‐related transgenic mice to further elucidate the role of physiological levels of eosinophils. RNA‐seq and cytokine array analyses were utilized to investigate the potential protective mechanisms of eosinophils. Results Compared to WT controls, Eos‐null mice exhibited significantly impaired HSC regeneration, characterized by a diminished response to 5‐fluorouracil (5‐FU) and carboplatin treatment. Both long‐term HSCs (LT‐HSCs) and lineage − Sca‐1 + c‐Kit + (LSK) demonstrated compromised reconstitution capacity in vivo and in vitro. HSCs from Eos‐null mice demonstrated elevated apoptosis under 5‐FU treatment, potentially due to the absence of eosinophil‐derived protective factors. Conversely, both chimeric mice and eosinophil incorporation within bone marrow transplantation systems significantly disrupted HSC homeostasis and function. Conclusion Physiological eosinophil level is essential for maintaining HSC regeneration, reconstitution capacity, and homeostasis. 10.1111/all.70021 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Physiological Level of Eosinophils Is Essential for the Regeneration and Homeostasis of Murine Hematopoietic Stem Cells
topic Allergy
url https://onlinelibrary.wiley.com/doi/10.1111/all.70021