The microbiota regulates hematopoietic stem and progenitor cell development by mediating inflammatory signals in the niche
Dan Zhong,
Haowei Jiang,
Chengzhuo Zhou,
Abrar Ahmed,
Hongji Li,
Xiaona Wei,
Qiuyu Lian,
Melodi Tastemel,
Hongyi Xin,
Mei Ge,
Chenhong Zhang,
Lili Jing
Affiliations
Dan Zhong
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China
Haowei Jiang
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Chengzhuo Zhou
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Abrar Ahmed
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Hongji Li
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Xiaona Wei
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Qiuyu Lian
UM-SJTU Joint Institute, Department of Automation, Shanghai Jiao Tong University, Shanghai 200240, China
Melodi Tastemel
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Hongyi Xin
Global Institute of Future Technology, Department of Automation, Shanghai Jiao Tong University, Shanghai 200240, China
Mei Ge
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Laiyi Center for Biopharmaceutical R&D, Shanghai 200240, China
Chenhong Zhang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Corresponding author
Lili Jing
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai 200240, China; Corresponding author
Summary: 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.
