1. P78Signalling via pi3k/foxo1a pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells
- Author
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Annamaria Kosztin, Zsuzsanna Lendvai, Gabor Foldes, B Merkely, Sian E. Harding, Judit Skopál, Thomas Leja, Domokos Máthé, and E Gara
- Subjects
Tube formation ,CD31 ,Programmed cell death ,Endothelium ,Physiology ,Angiogenesis ,Biology ,equipment and supplies ,Molecular biology ,Embryonic stem cell ,Cell biology ,Endothelial stem cell ,medicine.anatomical_structure ,Physiology (medical) ,embryonic structures ,medicine ,biological phenomena, cell phenomena, and immunity ,Cardiology and Cardiovascular Medicine ,reproductive and urinary physiology ,PI3K/AKT/mTOR pathway - Abstract
Purpose: 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. Methods: We studied PI3K-FOXO1A pathways during differentiation of H7 hESC towards endothelial lineage and on proliferation, maturation and cell death of hESC-derived endothelial cells (hESC-EC). We differentiated hESC towards endothelial lineage and used FACS to isolate CD31+ cells at day 13 after initiation of differentiation. Results: During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodelling-related genes. PI3K inhibitor LY294002 (10 μM) activated FOXO1A as shown by real-time PCR and nuclear translocation assay, and induced formation of CD31+ hESC-EC. In contrast, differentiating hESC with silenced FOXO1A by siRNA showed lower mRNA levels of CD31 and angiopoietin2. Similarly, overexpression of FOXO1A-eGFP construct in hESC-EC resulted in an increased angiopoietin2 expression (1.5-fold, p
- Published
- 2014
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