In vertebrates, myeloid cells arise from multiple waves of development： the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell（HSC） precursors and gives rise to myeloid cells t...In vertebrates, myeloid cells arise from multiple waves of development： the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell（HSC） precursors and gives rise to myeloid cells transiently during early development; whereas the second or adult wave of myelopoiesis emerges later from HSCs and produces myeloid cells continually during fetal and adult life. In the past decades, a great deal has been learnt about the development of myeloid cells from adult myelopoiesis, yet the genetic network governing embryonic myelopoiesis remains poorly defined. In this report, we present an in vivo study to delineate the role of Cebpa during zebrafish embryonic myelopoiesis. We show that embryonic myelopoiesis in cebpa-deficient zebrafish mutants initiates properly but fails to produce macrophages and neutrophils. The lack of macrophages and neutrophils in the mutants is largely attributed to the cell cycle arrest of embryonic myeloid progenitors, resulting in the impairment of their maintenance and subsequent differentiation. We further show that Cebpa, perhaps acting cooperatively with Runx1, plays a critical role in embryonic neutrophil maintenance. Our findings reveal a new role of Cebpa in embryonic myelopoiesis.展开更多
Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hemat...Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic traits.Each mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/lymphopoiesis.Our method should be applicable for other types of genetic screening in zebrafish.In addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 31271564, 31229003 and 31271574)the Team Program of Guangdong Natural Science Foundation (No. 2014A030312002)the Research Grants Council of the HKSAR (Nos. 663212, HKUST5/CRF/12R and AoE /M-09/12)
文摘In vertebrates, myeloid cells arise from multiple waves of development： the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell（HSC） precursors and gives rise to myeloid cells transiently during early development; whereas the second or adult wave of myelopoiesis emerges later from HSCs and produces myeloid cells continually during fetal and adult life. In the past decades, a great deal has been learnt about the development of myeloid cells from adult myelopoiesis, yet the genetic network governing embryonic myelopoiesis remains poorly defined. In this report, we present an in vivo study to delineate the role of Cebpa during zebrafish embryonic myelopoiesis. We show that embryonic myelopoiesis in cebpa-deficient zebrafish mutants initiates properly but fails to produce macrophages and neutrophils. The lack of macrophages and neutrophils in the mutants is largely attributed to the cell cycle arrest of embryonic myeloid progenitors, resulting in the impairment of their maintenance and subsequent differentiation. We further show that Cebpa, perhaps acting cooperatively with Runx1, plays a critical role in embryonic neutrophil maintenance. Our findings reveal a new role of Cebpa in embryonic myelopoiesis.
基金supported by the National Natural Science Foundation of China(Nos.30828020 and 31171403)the Human Talent Recruiting Funding from the Southern Medical University and Department of Education of Guangdong Province,China
文摘Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic traits.Each mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/lymphopoiesis.Our method should be applicable for other types of genetic screening in zebrafish.In addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.
