Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide

The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factor...

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Autores: Caballano-Infantes, E, Diaz, I, Hitos, AB, Cahuana, GM, Martinez-Ruiz, A, Soria-Juan, B, Rodriguez-Grinolo, R, Hmadcha, A, Martin, F, Soria, B, Tejedo, JR, Bedoya, FJ
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p7491
Acceso en línea:https://isabial.portalinvestigacion.com/publicaciones7491
Access Level:acceso abierto
Palabra clave:pluripotency
normoxia
nitric oxide
hypoxia
metabolism
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spelling Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric OxideCaballano-Infantes, EDiaz, IHitos, ABCahuana, GMMartinez-Ruiz, ASoria-Juan, BRodriguez-Grinolo, RHmadcha, AMartin, FSoria, BTejedo, JRBedoya, FJpluripotencynormoxianitric oxidehypoxiametabolismThe optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1 alpha and HIF-2 alpha) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones7491AntioxidantsISSN: 20763921reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p74912026-06-12T10:20:37Z
dc.title.none.fl_str_mv Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
title Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
spellingShingle Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
Caballano-Infantes, E
pluripotency
normoxia
nitric oxide
hypoxia
metabolism
title_short Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
title_full Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
title_fullStr Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
title_full_unstemmed Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
title_sort Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
dc.creator.none.fl_str_mv Caballano-Infantes, E
Diaz, I
Hitos, AB
Cahuana, GM
Martinez-Ruiz, A
Soria-Juan, B
Rodriguez-Grinolo, R
Hmadcha, A
Martin, F
Soria, B
Tejedo, JR
Bedoya, FJ
author Caballano-Infantes, E
author_facet Caballano-Infantes, E
Diaz, I
Hitos, AB
Cahuana, GM
Martinez-Ruiz, A
Soria-Juan, B
Rodriguez-Grinolo, R
Hmadcha, A
Martin, F
Soria, B
Tejedo, JR
Bedoya, FJ
author_role author
author2 Diaz, I
Hitos, AB
Cahuana, GM
Martinez-Ruiz, A
Soria-Juan, B
Rodriguez-Grinolo, R
Hmadcha, A
Martin, F
Soria, B
Tejedo, JR
Bedoya, FJ
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv pluripotency
normoxia
nitric oxide
hypoxia
metabolism
topic pluripotency
normoxia
nitric oxide
hypoxia
metabolism
description The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1 alpha and HIF-2 alpha) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones7491
url https://isabial.portalinvestigacion.com/publicaciones7491
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Antioxidants
ISSN: 20763921
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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