Volume 25, No 10, Oct 2015

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 25 Issue 10, October 2015: 1093-1107   |  Open Access

ORIGINAL ARTICLES

G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition

Panpan Zhang¹, Qiuping He¹, Dongbo Chen², Weixiao Liu³, Lu Wang¹, Chunxia Zhang¹, Dongyuan Ma¹, Wei Li³, Bing Liu² and Feng Liu¹

¹State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
²307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China
³State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Correspondence: Feng Liu, Tel: +86-10-64807307; Fax: +86-10-64807313(liuf@ioz.ac.cn)

In vertebrates, embryonic hematopoietic stem and progenitor cells (HSPCs) are derived from a subset of endothelial cells, the hemogenic endothelium (HE), through the endothelial-to-hematopoietic transition (EHT). Notch signaling is essential for HSPC development during embryogenesis across vertebrates. However, whether and how it regulates EHT remains unclear. Here, we show that G protein-coupled receptor 183 (Gpr183) signaling serves as an indispensable switch for HSPC emergence by repressing Notch signaling before the onset of EHT. Inhibition of Gpr183 significantly upregulates Notch signaling and abolishes HSPC emergence. Upon activation by its ligand 7α-25-OHC, Gpr183 recruits β-arrestin1 and the E3 ligase Nedd4 to degrade Notch1 in specified HE cells and then facilitates the subsequent EHT. Importantly, 7α-25-OHC stimulation promotes HSPC emergence in vivo and in vitro, providing an attractive strategy for enhancing the in vitro generation of functional HSPCs.

10.1038/cr.2015.109

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