Cargando…

PDGFD switches on stem cell endothelial commitment

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, Xuri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519648/
https://www.ncbi.nlm.nih.gov/pubmed/35859222
http://dx.doi.org/10.1007/s10456-022-09847-4
_version_ 1784799446947594240
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, Xuri
author_facet 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, Xuri
author_sort Lu, Weisi
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-022-09847-4.
format Online
Article
Text
id pubmed-9519648
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-95196482022-09-30 PDGFD switches on stem cell endothelial commitment 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, Xuri Angiogenesis Original Paper 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-022-09847-4. Springer Netherlands 2022-07-20 2022 /pmc/articles/PMC9519648/ /pubmed/35859222 http://dx.doi.org/10.1007/s10456-022-09847-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
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, Xuri
PDGFD switches on stem cell endothelial commitment
title PDGFD switches on stem cell endothelial commitment
title_full PDGFD switches on stem cell endothelial commitment
title_fullStr PDGFD switches on stem cell endothelial commitment
title_full_unstemmed PDGFD switches on stem cell endothelial commitment
title_short PDGFD switches on stem cell endothelial commitment
title_sort pdgfd switches on stem cell endothelial commitment
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9519648/
https://www.ncbi.nlm.nih.gov/pubmed/35859222
http://dx.doi.org/10.1007/s10456-022-09847-4
work_keys_str_mv AT luweisi pdgfdswitchesonstemcellendothelialcommitment
AT xupeipei pdgfdswitchesonstemcellendothelialcommitment
AT dengboxiong pdgfdswitchesonstemcellendothelialcommitment
AT zhangjianing pdgfdswitchesonstemcellendothelialcommitment
AT zhanying pdgfdswitchesonstemcellendothelialcommitment
AT linxianchai pdgfdswitchesonstemcellendothelialcommitment
AT xuxiangzhong pdgfdswitchesonstemcellendothelialcommitment
AT xiazhaoxia pdgfdswitchesonstemcellendothelialcommitment
AT yangxiaoxi pdgfdswitchesonstemcellendothelialcommitment
AT zengxiaoling pdgfdswitchesonstemcellendothelialcommitment
AT huanglijuan pdgfdswitchesonstemcellendothelialcommitment
AT xiebingbing pdgfdswitchesonstemcellendothelialcommitment
AT wangchenghu pdgfdswitchesonstemcellendothelialcommitment
AT wangshasha pdgfdswitchesonstemcellendothelialcommitment
AT kuanghaiqing pdgfdswitchesonstemcellendothelialcommitment
AT hanxianjing pdgfdswitchesonstemcellendothelialcommitment
AT moraantonio pdgfdswitchesonstemcellendothelialcommitment
AT caoyihai pdgfdswitchesonstemcellendothelialcommitment
AT jiangqin pdgfdswitchesonstemcellendothelialcommitment
AT lixuri pdgfdswitchesonstemcellendothelialcommitment