Primary cilia regulate hematopoietic stem and progenitor cell specification through Notch signaling in zebrafish

被引:45
|
作者
Liu, Zhibin [1 ,2 ,3 ]
Tu, Haiqing [4 ]
Kang, Yunsi [5 ]
Xue, Yuanyuan [1 ,2 ,3 ]
Ma, Dongyuan [1 ,2 ,3 ]
Zhao, Chengtian [5 ]
Li, Huiyan [4 ]
Wang, Lu [1 ,2 ,6 ,7 ,8 ]
Liu, Feng [1 ,2 ,3 ]
机构
[1] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China
[4] Natl Ctr Biomed Anal, State Key Lab Prote, Beijing 100850, Peoples R China
[5] Ocean Univ China, Inst Evolut & Marine Biodivers, Qingdao 266003, Shandong, Peoples R China
[6] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
[7] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin 300020, Peoples R China
[8] Peking Union Med Coll, Tianjin 300020, Peoples R China
基金
中国国家自然科学基金;
关键词
HEMOGENIC ENDOTHELIUM; DEFINITIVE HEMATOPOIESIS; HAEMOGENIC ENDOTHELIUM; AORTIC ENDOTHELIUM; DIFFERENTIATION; TRANSITION; FLOW; RECRUITMENT; EMERGENCE; PATHWAY;
D O I
10.1038/s41467-019-09403-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hematopoietic stem and progenitor cells (HSPCs) are capable of producing all mature blood lineages, as well as maintaining the self-renewal ability throughout life. The hairy-like organelle, cilium, is present in most types of vertebrate cells, and plays important roles in various biological processes. However, it is unclear whether and how cilia regulate HSPC development in vertebrates. Here, we show that cilia-specific genes, involved in primary cilia formation and function, are required for HSPC development, especially in hemogenic endothelium (HE) specification in zebrafish embryos. Blocking primary cilia formation or function by genetic or chemical manipulations impairs HSPC development. Mechanistically, we uncover that primary cilia in endothelial cells transduce Notch signal to the earliest HE for proper HSPC specification during embryogenesis. Altogether, our findings reveal a pivotal role of endothelial primary cilia in HSPC development, and may shed lights into in vitro directed differentiation of HSPCs.
引用
收藏
页数:11
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