Developmental investigation and functional exploration of dendritic cells in zebrafish

Abstract

Dendritic cells (DCs) are key cellular components of the immune system and perform critical functions in innate and acquired immunity. In mammals, it is generally believed that DCs are generated exclusively from hematopoietic stem cells (HSCs). In the first part of the thesis, by utilizing a temporal-spatial resolved fate-mapping system, we show that zebrafish DCs arise from two sources: dorsal aorta-born endothelium-derived hematopoietic progenitors (EHPs) and HSCs. The EHP-derived DCs emerge early and predominantly colonize the developing thymus during larval stages and gradually diminish in juvenile stages. In contrast, the HSC-derived DCs emerge later and are capable of populating various tissues from late larval stages to adulthood. We further document that the EHP- and HSC-derived DCs display different dependencies on Fms-like tyrosine kinase 3 (flt3), a receptor tyrosine kinase known to be essential for DC development in mammals. In the second part of the thesis, we explore the function of a unique HSC-derived population of DCs specifically resident in the myelin-rich white matter of the brain. We set up a demyelination-remyelination pathological model in adult zebrafish and found that the brain-resident DCs show successive morphological changes during demyelination and remyelination. However, the transcriptome of the brain-resident DCs does not change significantly during demyelination, and the loss of these cells does not alter the pathological process, suggesting that they are dispensable for the progression of demyelination and remyelination.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Shangyu DANG (Supervisor) & Zilong WEN (Supervisor)