1. The microbiota regulates hematopoietic stem and progenitor cell development by mediating inflammatory signals in the niche.
- Author
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Zhong, Dan, Jiang, Haowei, Zhou, Chengzhuo, Ahmed, Abrar, Li, Hongji, Wei, Xiaona, Lian, Qiuyu, Tastemel, Melodi, Xin, Hongyi, Ge, Mei, Zhang, Chenhong, and Jing, Lili
- Abstract
The commensal microbiota regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) in bone marrow. Whether and how the microbiota influences HSPC development during embryogenesis is unclear. Using gnotobiotic zebrafish, we show that the microbiota is necessary for HSPC development and differentiation. Individual bacterial strains differentially affect HSPC formation, independent of their effects on myeloid cells. Early-life dysbiosis in chd8
−/− zebrafish impairs HSPC development. Wild-type microbiota promote HSPC development by controlling basal inflammatory cytokine expression in kidney niche, and chd8−/− commensals elicit elevated inflammatory cytokines that reduce HSPCs and enhance myeloid differentiation. We identify an Aeromonas veronii strain with immuno-modulatory activities that fails to induce HSPC development in wild-type fish but selectively inhibits kidney cytokine expression and rebalances HSPC development in chd8−/− zebrafish. Our studies highlight the important roles of a balanced microbiome during early HSPC development that ensure proper establishment of lineal precursor for adult hematopoietic system. [Display omitted] • Microbiota depletion impairs HSPC development during embryogenesis in zebrafish • Disturbed microbiota in chd8−/− decreases HSPC formation and promotes myelopoiesis • Different strains induce different levels of cytokine expression in HSPC niche • Local cytokine expression controls HSPC formation and myeloid differentiation Zhong et al. show that commensal microbiota regulates normal HSPC development by mediating appropriate inflammatory cytokine expression in HSPC niche. The microbiota of chd8−/− zebrafish induces enhanced cytokine expression and impairs HSPC development. An Aeromonas strain selectively suppresses excessive cytokines in HSPC niche and restores HSPC development in chd8−/− zebrafish. [ABSTRACT FROM AUTHOR]- Published
- 2023
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