| Autor: |
Merkely B; 1 Heart and Vascular Center, Semmelweis University , Budapest, Hungary ., Gara E, Lendvai Z, Skopál J, Leja T, Zhou W, Kosztin A, Várady G, Mioulane M, Bagyura Z, Németh T, Harding SE, Földes G |
| Jazyk: |
angličtina |
| Zdroj: |
Stem cells and development [Stem Cells Dev] 2015 Apr 01; Vol. 24 (7), pp. 869-78. Date of Electronic Publication: 2014 Dec 22. |
| DOI: |
10.1089/scd.2014.0247 |
| Abstrakt: |
Vascular derivatives of human embryonic stem cells (hESC) are being developed as sources of tissue-specific cells for organ regeneration. However, identity of developmental pathways that modulate the specification of endothelial cells is not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward endothelial lineage and on proliferation, maturation, and cell death of hESC-derived endothelial cells (hESC-EC). During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodeling-related genes. PI3K inhibitor LY294002 activated FOXO1A and induced formation of CD31(+) hESC-EC. In contrast, differentiating hESC with silenced FOXO1A by small interfering RNA (siRNA) showed lower mRNA levels of CD31 and angiopoietin2. LY294002 decreased proliferative activity of purified hESC-EC, while FOXO1A siRNA increased their proliferation. LY294002 inhibits migration and tube formation of hESC-EC; in contrast, FOXO1A siRNA increased in vitro tube formation activity of hESC-EC. After in vivo conditioning of cells in athymic nude rats, cells retain their low FOXO1A expression levels. PI3K/FOXO1A pathway is important for function and survival of hESC-EC and in the regulation of endothelial cell fate. Understanding these properties of hESC-EC may help in future applications for treatment of injured organs. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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