Long-Term Hypoxia Maintains a State of Dedifferentiation and Enhanced Stemness in Fetal Cardiovascular Progenitor Cells

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, a...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2021-09, Vol.22 (17), p.9382
Main Authors: Knox, Cole, Camberos, Victor, Ceja, Lourdes, Monteon, Andrea, Hughes, Lorelei, Longo, Lawrence, Kearns-Jonker, Mary
Format: Article
Language:English
Subjects:
AKT protein
Apoptosis
cardiovascular progenitor cells
Cardiovascular system
Cell cycle
Cell differentiation
Cloning
Embryos
Fetuses
Flow cytometry
Gene expression
Gestation
High altitude
Hypoxia
Islet-1
Islet-1 protein
Kinases
ovine
Oxidative stress
Oxygen tension
Phosphorylation
Polymerase chain reaction
Progenitor cells
Stem cells
stemness
Survival
Western blotting
Wnt protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22179382