Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells

Fetal neural stem cells (NSCs) physiologically reside under low-oxygen conditions (1%–5% of tissue pO2), but are often transferred and maintained under atmospheric oxygen levels of 21% pO2 (hyperoxia) for in vitro investigations. These altered oxygen conditions lead to adaptive changes in NSCs which...

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Main Authors: Jennifer Lanto, Monika Maria Nicole Vehlken, Valeriia Abramenko, Alexander Storch, Franz Markert
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1546131/full
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author Jennifer Lanto
Monika Maria Nicole Vehlken
Valeriia Abramenko
Alexander Storch
Alexander Storch
Franz Markert
author_facet Jennifer Lanto
Monika Maria Nicole Vehlken
Valeriia Abramenko
Alexander Storch
Alexander Storch
Franz Markert
author_sort Jennifer Lanto
collection DOAJ
description Fetal neural stem cells (NSCs) physiologically reside under low-oxygen conditions (1%–5% of tissue pO2), but are often transferred and maintained under atmospheric oxygen levels of 21% pO2 (hyperoxia) for in vitro investigations. These altered oxygen conditions lead to adaptive changes in NSCs which complicate the interpretation of in vitro data. However, the underlying adaption dynamics remain largely enigmatic. Here we investigated short-term hyperoxia effects (5 days in 3% pO2 followed by 2 days in 21% pO2) in comparison to continuous hyperoxia effects (7 days in 21% pO2) and physioxic control (7 days in 3% pO2). We utilized cortical NSCs to analyze the cell cycle phases by flow cytometry and cumulative BrdU incorporation assay. NSCs showed a severe reduction of cell proliferation when cultivated under continuous hyperoxia, but no changes after short-term hyperoxia. Subsequent cell cycle analysis as assessed by flow cytometry revealed a clear shift of NSCs from G0/G1-phase towards S- or G2/M-phase after both continuous and short-term hyperoxia. However, while cell cycle length was dramatically reduced by short-term hyperoxia, it was increased during continuous hyperoxia. Taken together, our results demonstrate the beneficial effect of physioxia for expanding NSCs in vitro and reveal differential effects of short-term hyperoxia compared to continuous hyperoxia.
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spelling doaj-art-e6b6dd70bcd14939a8d317855c411bdc2025-01-28T06:41:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011310.3389/fcell.2025.15461311546131Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cellsJennifer Lanto0Monika Maria Nicole Vehlken1Valeriia Abramenko2Alexander Storch3Alexander Storch4Franz Markert5Department of Neurology, University of Rostock, Rostock, GermanyDepartment of Neurology, University of Rostock, Rostock, GermanyDepartment of Neurology, University of Rostock, Rostock, GermanyDepartment of Neurology, University of Rostock, Rostock, GermanyGerman Centre for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, GermanyDepartment of Neurology, University of Rostock, Rostock, GermanyFetal neural stem cells (NSCs) physiologically reside under low-oxygen conditions (1%–5% of tissue pO2), but are often transferred and maintained under atmospheric oxygen levels of 21% pO2 (hyperoxia) for in vitro investigations. These altered oxygen conditions lead to adaptive changes in NSCs which complicate the interpretation of in vitro data. However, the underlying adaption dynamics remain largely enigmatic. Here we investigated short-term hyperoxia effects (5 days in 3% pO2 followed by 2 days in 21% pO2) in comparison to continuous hyperoxia effects (7 days in 21% pO2) and physioxic control (7 days in 3% pO2). We utilized cortical NSCs to analyze the cell cycle phases by flow cytometry and cumulative BrdU incorporation assay. NSCs showed a severe reduction of cell proliferation when cultivated under continuous hyperoxia, but no changes after short-term hyperoxia. Subsequent cell cycle analysis as assessed by flow cytometry revealed a clear shift of NSCs from G0/G1-phase towards S- or G2/M-phase after both continuous and short-term hyperoxia. However, while cell cycle length was dramatically reduced by short-term hyperoxia, it was increased during continuous hyperoxia. Taken together, our results demonstrate the beneficial effect of physioxia for expanding NSCs in vitro and reveal differential effects of short-term hyperoxia compared to continuous hyperoxia.https://www.frontiersin.org/articles/10.3389/fcell.2025.1546131/fulloxygenneural stem cellshypoxiahyperoxiaphysioxiacortex
spellingShingle Jennifer Lanto
Monika Maria Nicole Vehlken
Valeriia Abramenko
Alexander Storch
Alexander Storch
Franz Markert
Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
Frontiers in Cell and Developmental Biology
oxygen
neural stem cells
hypoxia
hyperoxia
physioxia
cortex
title Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
title_full Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
title_fullStr Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
title_full_unstemmed Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
title_short Hyperoxia shows duration-dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
title_sort hyperoxia shows duration dependent effects on the lengths of cell cycle phases in fetal cortical neural stem cells
topic oxygen
neural stem cells
hypoxia
hyperoxia
physioxia
cortex
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1546131/full
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