The ontogeny and heterogeneity of myeloid cells across zebrafish organs

Abstract

Myeloid cells play essential roles in immune response, homeostasis maintenance, and tissue remodeling. These diverse functions could be implemented by phenotypically and functionally distinct myeloid subpopulations, and it is thus vital to clearly delineate the heterogeneity of myeloid cells with discriminative markers to study their functions. In this thesis project, we comprehensively profiled the ontogeny and heterogeneity of myeloid cells across zebrafish organs. We discovered a novel non-hematopoiesis-derived myeloid cell population, metaphocytes, in zebrafish barrier tissues (epidermis, gill, and intestine). Notably, metaphocytes do not possess canonical myeloid cell functions such as phagocytosis but instead are capable of sampling external soluble antigens, thereby regulating mucosal immunity. Furthermore, we also identified two distinct macrophage subsets, the lgals3bpb⁺ pro-inflammatory macrophages with prominent phagocytosis-related gene signatures and the ccl34a.4⁺ pro-remodeling macrophages with marked tissue remodeling/regeneration-related gene modules, in all peripheral organs (barrier tissues, liver, and heart). In parallel, conventional dendritic cells (cDCs) with prominent antigen presentation capacity and plasmacytoid dendritic cells (pDCs) featured with conserved anti-virus properties are also observed across peripheral organs. Interestingly, two distinct cDC subpopulations were identified in zebrafish brain parenchyma. Finally, we generated specific reporter lines for in vivo tracking of metaphocytes, macrophage and DC subsets based on their discriminative marker genes. Our study depicts the landscape of the heterogeneous myeloid cell populations in adult zebrafish and creates valuable tools for in-depth ontogenic and functional study of these cells in zebrafish.

Date of Award	2023
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Zilong WEN (Supervisor)