Multiple waves of T lymphopoiesis and characterization of hemogenic endothelium in zebrafish

Abstract

T lymphocytes are key cellular components of adaptive immune system in vertebrates. Despite their heterogeneities, it is believed that all different types of T lymphocytes are generated exclusively via the differentiation of hematopoietic stem cells (HSCs). By temporal-spatial resolved fate mapping analysis, here we show that the zebrafish aorta-gonad-mesonephros (AGM) and posterior blood island (PBI), the hematopoietic tissues previously known to generate HSCs and erythro-myeloid progenitors (EMPs), respectively, gives rise to a transient wave of HSC-independent T lymphopoiesis, which occurs early and generates predominantly CD4 T_αβ cells exclusively in the larval stage. In contrast, HSC-derived T lymphopoiesis emerges later and produces various subtypes of T lymphocytes continuously from the larval stage to adulthood. Both two waves of T lymphopoiesis are originated from hemogenic endothelium (HEs) via endothelial-hematopoietic transition (EHT). Further characterization of HEs in zebrafish from 28 hours-post-fertilization shows that the vast majority of ventral endothelium of aorta in both AGM and PBI are hemogenic and undergo EHT before 3 days-post-fertilization, while dorsal wall of aorta contains only ordinary endothelium (OEs) without hemogenic potential, indicating that HEs and OEs are distributed in a spatial-separated manner. Our study unveils the existence, origin and ontogeny of HSC-independent T lymphopoiesis in vivo, as well as systematically characterizes the distribution and dynamics of HEs during embryonic definitive hematopoiesis.

Date of Award	2019
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology