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BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway.

ABSTRACT: The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum-free condition, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. BMP4 promoted hESC differentiation into CD34+CD31+ cells at an early stage. In contrast, TGFbeta suppressed BMP4-induced CD34+CD31+ cell development, and promoted CD34+CD31- cells that failed to give rise to either endothelial or smooth muscle cells. The BMP-Smad inhibitor, dorsomorphin, inhibited phosphorylation of Smad1/5/8, and blocked hESC differentiation to CD34+CD31+ progenitor cells, suggesting that BMP Smad-dependent signaling is critical for CD34+CD31+ vascular progenitor development. Our findings provide new insight into how pluripotent hESCs differentiate into vascular cells.

SUBMITTER: Bai H

PROVIDER: S-EPMC3065830 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway.

Bai Hao H Gao Yongxing Y Arzigian Melanie M Wojchowski Don M DM Wu Wen-Shu WS Wang Zack Z ZZ

Journal of cellular biochemistry 20100201 2

The signals that direct pluripotent stem cell differentiation into lineage-specific cells remain largely unknown. Here, we investigated the roles of BMP on vascular progenitor development from human embryonic stem cells (hESCs). In a serum-free condition, hESCs sequentially differentiated into CD34+CD31-, CD34+CD31+, and then CD34-CD31+ cells during vascular cell development. CD34+CD31+ cells contained vascular progenitor population that gives rise to endothelial cells and smooth muscle cells. B ...[more]

PMID: 19950207

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Project description:Chordin-like 1 (CHRDL1) is a secreted glycoprotein with repeated cysteine-rich domains, which can bind to BMPs family ligands. Although it has been reported to play important roles in several systems, the exact roles of CHRDL1 on human bone mesenchymal stem cells (hBMSCs) osteogenesis remain to be explored. The present study aimed to investigate the roles of CHRDL1 on the osteogenic differentiation of hBMSCs and the underlying molecular mechanisms. We found that CHRDL1 was upregulated during hBMSCs osteogenesis, and rhBMP-4 administration could enhance CHRDL1 mRNA expression in a dose and time dependent manner. Knockdown of CHRDL1 did not affect hBMSCs proliferation, but inhibited the BMP-4-dependent osteogenic differentiation, showing decreased mRNA expression levels of osteogenic markers and reduced mineralization. On the contrary, overexpression of CHRDL1 enhanced BMP-4 induced osteogenic differentiation of hBMSCs. Moreover, in vivo experiments by transplanting CHRDL1 gene modified hBMSCs into nude mice defective femur models displayed higher new bone formation in CHRDL1 overexpression groups, but lower new bone formation in CHRDL1 knockdown groups, compared with control groups. In consistent with the bone formation rate, there were increased CHRDL1 protein expression in new bone formation regions of defective femur in CHRDL1 overexpression groups, while reduced CHRDL1 protein expression in CHRDL1 knockdown groups compared with control groups. These indicate that CHRDL1 can promote osteoblast differentiation in vivo. Furthermore, the mechanisms study showed that CHRDL1 improved BMP-4 induced phosphorylation of SMAD1/5/9 during osteogenic differentiation of hBMSCs. Besides, promotion of osteogenic differentiation and the activation of SMAD phosphorylation by CHRDL1 can be blocked by BMP receptor type I inhibitor LDN-193189. In conclusion, our results suggested that CHRDL1 can promote hBMSCs osteogenic differentiation through enhancing the activation of BMP-4-SMAD1/5/9 pathway.

Dataset Information

BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway.

Publications

BMP4 regulates vascular progenitor development in human embryonic stem cells through a Smad-dependent pathway.

Similar Datasets

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