PDGFD switches on stem cell endothelial commitment
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Published:2022-07-20
Issue:4
Volume:25
Page:517-533
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ISSN:0969-6970
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Container-title:Angiogenesis
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language:en
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Short-container-title:Angiogenesis
Author:
Lu Weisi, Xu Peipei, Deng Boxiong, Zhang Jianing, Zhan Ying, Lin Xianchai, Xu Xiangzhong, Xia Zhaoxia, Yang Xiaoxi, Zeng Xiaoling, Huang Lijuan, Xie Bingbing, Wang Chenghu, Wang Shasha, Kuang Haiqing, Han Xianjing, Mora Antonio, Cao Yihai, Jiang Qin, Li XuriORCID
Abstract
AbstractThe critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.
Funder
Program of Guangzhou Scientific Research Plan Natural Science Foundation of Guangdong Province The Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Guangzhou Basic and Applied Research Program National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Clinical Biochemistry,Physiology
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