THESIS
2023
1 online resource (xvii, 122 pages) : illustrations (chiefly color)
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 mu...[
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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.
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