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Open Access 20-07-2022 | Original Paper

PDGFD switches on stem cell endothelial commitment

Authors: Weisi Lu, Peipei Xu, Boxiong Deng, Jianing Zhang, Ying Zhan, Xianchai Lin, Xiangzhong Xu, Zhaoxia Xia, Xiaoxi Yang, Xiaoling Zeng, Lijuan Huang, Bingbing Xie, Chenghu Wang, Shasha Wang, Haiqing Kuang, Xianjing Han, Antonio Mora, Yihai Cao, Qin Jiang, Xuri Li

Published in: Angiogenesis | Issue 4/2022

Abstract

The 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.

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Title: PDGFD switches on stem cell endothelial commitment
Authors: Weisi Lu
Peipei Xu
Boxiong Deng
Jianing Zhang
Ying Zhan
Xianchai Lin
Xiangzhong Xu
Zhaoxia Xia
Xiaoxi Yang
Xiaoling Zeng
Lijuan Huang
Bingbing Xie
Chenghu Wang
Shasha Wang
Haiqing Kuang
Xianjing Han
Antonio Mora
Yihai Cao
Qin Jiang
Xuri Li
Publication date: 20-07-2022
Publisher: Springer Netherlands
Published in: Angiogenesis / Issue 4/2022
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-022-09847-4

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