Cebpa regulates myeloid progenitors and neutrophil development during zebrafish embryonic myelopoiesis

Abstract

In vertebrates, myeloid cells can be derived from multiple waves of myelopoiesis: the primitive or embryonic wave originates from hematopoietic progenitors during the early development stages and gives rise to myeloid cells transiently; whereas the definitive or adult wave of myelopoiesis initiates from Hematopoietic Stem Cells (HSCs) at later stages and produces myeloid cell lineages throughout the life span of organisms. In the past decades, numerous studies have been performed to explore the development of adult myelopoiesis derived myeloid cells. However, the genetic network governing embryonic myelopoiesis remains poorly defined. In this thesis, we present an in vivo study to delineate the role of Cebpα during zebrafish embryonic myelopoiesis. Via ENU forward genetic screening, We identified a cebpα^hkz7 mutant zebrafish, in which the mutation results in a truncated dysfunction Cebpα protein. Phenotype characterization shows that embryonic myelopoiesis is initiated properly but fails to generate mature macrophages and neutrophils in cebpα-deficiency zebrafish embryos. Further cell cycle and cell death analysis indicates that the absence of macrophages and neutrophils in the mutants is attributed to the cell cycle arrest of embryonic myeloid progenitors in S phase, thereby blocking their maintenance and subsequent differentiation. Besides, We find that Cebpα can cooperate with Runx1 to regulate embryonic neutrophil maintenance. To sum up, Our findings reveal a new role of Cebpα in embryonic myelopoiesis.

Date of Award	2016
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology