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Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes
BACKGROUND: Fetal hypoxia causes vital, systemic, developmental malformations in the fetus, particularly in the brain, and increases the risk of diseases in later life. We previously demonstrated that fetal hypoxia exposure increases the susceptibility of the neonatal brain to hypoxic-ischemic insul...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022003/ https://www.ncbi.nlm.nih.gov/pubmed/36932456 http://dx.doi.org/10.1186/s13578-023-01012-8 |
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author | Kremsky, Isaac Ma, Qingyi Li, Bo Dasgupta, Chiranjib Chen, Xin Ali, Samir Angeloni, Shawnee Wang, Charles Zhang, Lubo |
author_facet | Kremsky, Isaac Ma, Qingyi Li, Bo Dasgupta, Chiranjib Chen, Xin Ali, Samir Angeloni, Shawnee Wang, Charles Zhang, Lubo |
author_sort | Kremsky, Isaac |
collection | PubMed |
description | BACKGROUND: Fetal hypoxia causes vital, systemic, developmental malformations in the fetus, particularly in the brain, and increases the risk of diseases in later life. We previously demonstrated that fetal hypoxia exposure increases the susceptibility of the neonatal brain to hypoxic-ischemic insult. Herein, we investigate the effect of fetal hypoxia on programming of cell-specific transcriptomes in the brain of neonatal rats. RESULTS: We obtained RNA sequencing (RNA-seq) data from neurons, microglia, oligodendrocytes, A2B5(+) oligodendrocyte precursor cells, and astrocytes from male and female neonatal rats subjected either to fetal hypoxia or control conditions. Substantial transcriptomic responses to fetal hypoxia occurred in neurons, microglia, oligodendrocytes, and A2B5(+) cells. Not only were the transcriptomic responses unique to each cell type, but they also occurred with a great deal of sexual dimorphism. We validated differential expression of several genes related to inflammation and cell death by Real-time Quantitative Polymerase Chain Reaction (qRT-PCR). Pathway and transcription factor motif analyses suggested that the NF-kappa B (NFκB) signaling pathway was enriched in the neonatal male brain due to fetal hypoxia, and we verified this result by transcription factor assay of NFκB-p65 in whole brain. CONCLUSIONS: Our study reveals a significant impact of fetal hypoxia on the transcriptomes of neonatal brains in a cell-specific and sex-dependent manner, and provides mechanistic insights that may help explain the development of hypoxic-ischemic sensitive phenotypes in the neonatal brain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01012-8. |
format | Online Article Text |
id | pubmed-10022003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-100220032023-03-18 Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes Kremsky, Isaac Ma, Qingyi Li, Bo Dasgupta, Chiranjib Chen, Xin Ali, Samir Angeloni, Shawnee Wang, Charles Zhang, Lubo Cell Biosci Research BACKGROUND: Fetal hypoxia causes vital, systemic, developmental malformations in the fetus, particularly in the brain, and increases the risk of diseases in later life. We previously demonstrated that fetal hypoxia exposure increases the susceptibility of the neonatal brain to hypoxic-ischemic insult. Herein, we investigate the effect of fetal hypoxia on programming of cell-specific transcriptomes in the brain of neonatal rats. RESULTS: We obtained RNA sequencing (RNA-seq) data from neurons, microglia, oligodendrocytes, A2B5(+) oligodendrocyte precursor cells, and astrocytes from male and female neonatal rats subjected either to fetal hypoxia or control conditions. Substantial transcriptomic responses to fetal hypoxia occurred in neurons, microglia, oligodendrocytes, and A2B5(+) cells. Not only were the transcriptomic responses unique to each cell type, but they also occurred with a great deal of sexual dimorphism. We validated differential expression of several genes related to inflammation and cell death by Real-time Quantitative Polymerase Chain Reaction (qRT-PCR). Pathway and transcription factor motif analyses suggested that the NF-kappa B (NFκB) signaling pathway was enriched in the neonatal male brain due to fetal hypoxia, and we verified this result by transcription factor assay of NFκB-p65 in whole brain. CONCLUSIONS: Our study reveals a significant impact of fetal hypoxia on the transcriptomes of neonatal brains in a cell-specific and sex-dependent manner, and provides mechanistic insights that may help explain the development of hypoxic-ischemic sensitive phenotypes in the neonatal brain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13578-023-01012-8. BioMed Central 2023-03-17 /pmc/articles/PMC10022003/ /pubmed/36932456 http://dx.doi.org/10.1186/s13578-023-01012-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kremsky, Isaac Ma, Qingyi Li, Bo Dasgupta, Chiranjib Chen, Xin Ali, Samir Angeloni, Shawnee Wang, Charles Zhang, Lubo Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title | Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title_full | Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title_fullStr | Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title_full_unstemmed | Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title_short | Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
title_sort | fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022003/ https://www.ncbi.nlm.nih.gov/pubmed/36932456 http://dx.doi.org/10.1186/s13578-023-01012-8 |
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