Hypoxia induces re‐entry of committed cells into pluripotency

ABSTRACT Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as w...

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Veröffentlicht in:Stem cells (Dayton, Ohio) Ohio), 2013-09, Vol.31 (9), p.1737-1748
Hauptverfasser: Mathieu, Julie, Zhang, Zhan, Nelson, Angelique, Lamba, Deepak A., Reh, Thomas A., Ware, Carol, Ruohola‐Baker, Hannele
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container_end_page 1748
container_issue 9
container_start_page 1737
container_title Stem cells (Dayton, Ohio)
container_volume 31
creator Mathieu, Julie
Zhang, Zhan
Nelson, Angelique
Lamba, Deepak A.
Reh, Thomas A.
Ware, Carol
Ruohola‐Baker, Hannele
description ABSTRACT Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self‐renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC‐ or iPSC‐derived differentiated cells back to a stem cell‐like state, as evidenced by re‐activation of an Oct4‐promoter reporter. Hypoxia‐induced “de‐differentiated” cells also mimic hESCs in their morphology, long‐term self‐renewal capacity, genome‐wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1–60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function. Stem Cells 2013;31:1737‐1748
doi_str_mv 10.1002/stem.1446
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Adult
Animals
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biomarkers - metabolism
Cell Dedifferentiation - drug effects
Cell Hypoxia - drug effects
Cell Line
Cell Lineage - drug effects
dedifferentiation
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Embryos
Green Fluorescent Proteins - metabolism
hESC
Histone Deacetylases - metabolism
Human embryonic stem cell
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Mice
Models, Biological
niche
Octamer Transcription Factor-3 - metabolism
Oxygen - pharmacology
Plasticity
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - drug effects
Pluripotent Stem Cells - metabolism
Stem cell fate
Stem cells
title Hypoxia induces re‐entry of committed cells into pluripotency
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