Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells
| Autor: | Mary Kearns-Jonker, Lorelei Hughes, Lawrence D. Longo, Victor Camberos, Cole Knox, Andrea Monteon, Lourdes Ceja |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
QH301-705.5
Cell Survival Cell LIM-Homeodomain Proteins Biology Cardiovascular System Catalysis Article cardiovascular progenitor cells Inorganic Chemistry stemness Phosphatidylinositol 3-Kinases Cell Movement Pregnancy medicine Animals Physical and Theoretical Chemistry Progenitor cell Biology (General) Islet-1 Molecular Biology Protein kinase B QD1-999 Spectroscopy YAP1 Sheep hypoxia Stem Cells Organic Chemistry Cell Cycle Wnt signaling pathway Cell Differentiation General Medicine Hypoxia (medical) Cell Hypoxia Computer Science Applications Cell biology Chemistry ovine medicine.anatomical_structure Female medicine.symptom Stem cell Signal transduction Proto-Oncogene Proteins c-akt Transcription Factors |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9382, p 9382 (2021) Volume 22 Issue 17 |
| ISSN: | 1422-0067 |
| Popis: | Early-stage mammalian embryos survive within a low oxygen tension environment and develop into fully functional, healthy organisms despite this hypoxic stress. This suggests that hypoxia plays a regulative role in fetal development that influences cell mobilization, differentiation, proliferation, and survival. The long-term hypoxic environment is sustained throughout gestation. Elucidation of the mechanisms by which cardiovascular stem cells survive and thrive under hypoxic conditions would benefit cell-based therapies where stem cell survival is limited in the hypoxic environment of the infarcted heart. The current study addressed the impact of long-term hypoxia on fetal Islet-1+ cardiovascular progenitor cell clones, which were isolated from sheep housed at high altitude. The cells were then cultured in vitro in 1% oxygen and compared with control Islet-1+ cardiovascular progenitor cells maintained at 21% oxygen. RT-PCR, western blotting, flow cytometry, and migration assays evaluated adaptation to long term hypoxia in terms of survival, proliferation, and signaling. Non-canonical Wnt, Notch, AKT, HIF-2α and Yap1 transcripts were induced by hypoxia. The hypoxic niche environment regulates these signaling pathways to sustain the dedifferentiation and survival of fetal cardiovascular progenitor cells. |
| Databáze: | OpenAIRE |
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