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

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 vertebrat...

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Main Authors:	Zhang, Panpan, He, Qiuping, Chen, Dongbo, Liu, Weixiao, Wang, Lu, Zhang, Chunxia, Ma, Dongyuan, Li, Wei, Liu, Bing, Liu, Feng
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650626/

id	pubmed-4650626
recordtype	oai_dc
spelling	pubmed-46506262015-12-01 G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition Zhang, Panpan He, Qiuping Chen, Dongbo Liu, Weixiao Wang, Lu Zhang, Chunxia Ma, Dongyuan Li, Wei Liu, Bing Liu, Feng Original Article 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. Nature Publishing Group 2015-10 2015-09-11 /pmc/articles/PMC4650626/ /pubmed/26358189 http://dx.doi.org/10.1038/cr.2015.109 Text en Copyright © 2015 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences http://creativecommons.org/licenses/by-nc-sa/4.0/ This license allows readers to copy, distribute and transmit the Contributionas long as it attributed back to the author. Readers are permitted to alter, transform or build upon the Contribution as long as the resulting work is then distributed under this is a similar license. Readers are notpermitted touse theContributionfor commercial purposes. Please read the full license for further details at - http://creativecommons.org/licenses/by-nc-sa/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Panpan He, Qiuping Chen, Dongbo Liu, Weixiao Wang, Lu Zhang, Chunxia Ma, Dongyuan Li, Wei Liu, Bing Liu, Feng
spellingShingle	Zhang, Panpan He, Qiuping Chen, Dongbo Liu, Weixiao Wang, Lu Zhang, Chunxia Ma, Dongyuan Li, Wei Liu, Bing Liu, Feng G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
author_facet	Zhang, Panpan He, Qiuping Chen, Dongbo Liu, Weixiao Wang, Lu Zhang, Chunxia Ma, Dongyuan Li, Wei Liu, Bing Liu, Feng
author_sort	Zhang, Panpan
title	G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
title_short	G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
title_full	G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
title_fullStr	G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
title_full_unstemmed	G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition
title_sort	g protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via notch1 inhibition
description	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.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650626/
_version_	1613503152723591168

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

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