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Differentiation Kinetics of Hematopoietic Stem and Progenitor Cells In Vivo Are Not Affected by β-Glucan Treatment in Trained Immunity

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Abstract

Agonists of trained immunity induce epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) to generate long-lasting immune protection. Although trained HSPCs generate myeloid cells with increased responsiveness to secondary challenges, whether their differentiation kinetics is affected by prior exposure to inducers of trained immunity remains elusive. Here, we used lineage tracing to examine the cell fates of endothelial protein C receptor-positive hematopoietic stem cells (EPCR+ HSCs) and fms-like tyrosine kinase 3-positive multipotent progenitor cells (Flt3+ MPPs) in β-glucan-induced trained immunity. We found that although β-glucan triggered the expected expansion of myeloid progenitors, the differentiation behaviors of EPCR+ HSCs and Flt3+ MPPs in multiple cycles of hematopoietic regeneration were hardly affected. Thus, our results rule out changed kinetics in cell differentiation by EPCR+ HSC and Flt3+ MPP as the cause of enhanced myelopoiesis upon secondary immune challenges.

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Acknowledgements

The authors would like to thank Dr. Yi Zeng for the Procr-CreER mouse line and Dr. Fernando Camargo for the Flt3-CreER mouse line, members of the Sun group for discussion and support, the Molecular and Cell Biology Core Facility (MCBCF) and Animal Core Facility at the School of Life Science and Technology, ShanghaiTech University, and the Animal Facility at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Lab, Shanghai Advanced Research Institute, Chinese Academy of Science for providing technical service.

Funding

This work was supported by the National Key R&D Program of China (2020YFA0710801) and the National Natural Science Foundation of China (81970102).

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  1. School of Life Science and Technology, ShanghaiTech University, Shanghai, China

    Feiyang Li & Jianlong Sun

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J. Sun and F. Li designed the experiments. F. Li performed the experiment. F. Li and J. Sun analyzed the data and wrote the manuscript.

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Correspondence to Jianlong Sun.

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Li, F., Sun, J. Differentiation Kinetics of Hematopoietic Stem and Progenitor Cells In Vivo Are Not Affected by β-Glucan Treatment in Trained Immunity. Inflammation 46, 718–729 (2023). https://doi.org/10.1007/s10753-022-01767-1

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