Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.
Fetal hypoxia results in sex- and cell type-specific alterations in neonatal transcription in rat oligodendrocyte precursor cells, microglia, neurons, and oligodendrocytes.
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DOI：
10.1186/s13578-023-01012-8
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发表时间：
2023-03-17
影响因子：
7.5
通讯作者：
Zhang, Lubo
中科院分区：
文献类型：
--
作者：
Kremsky, Isaac;Ma, Qingyi;Li, Bo;Dasgupta, Chiranjib;Chen, Xin;Ali, Samir;Angeloni, Shawnee;Wang, Charles;Zhang, Lubo
胎儿缺氧会导致胎儿，特别是大脑的重大、全身性发育畸形，并增加以后生活中患病的风险。我们之前已经证明，胎儿缺氧暴露会增加新生儿大脑对缺氧缺血性损伤的易感性。在此，我们研究了胎儿缺氧对新生大鼠大脑中细胞特异性转录组编程的影响。我们获得了来自雄性和雌性新生大鼠的神经元、小胶质细胞、少突胶质细胞、A2B5+少突胶质细胞前体细胞和星形胶质细胞的RNA测序（RNA-seq）数据，这些大鼠分别受到胎儿缺氧或对照条件的影响。胎儿缺氧发生在神经元、小胶质细胞、少突胶质细胞和A2B5+细胞中。不仅每种细胞类型的转录组反应是独特的，而且它们还与大量的两性二态性一起发生。我们通过实时定量聚合酶链反应（qRT-PCR）验证了几种与炎症和细胞死亡相关的基因的差异表达。通路和转录因子基序分析表明，胎儿缺氧导致新生儿雄性大脑中nf - κB （NFκB）信号通路富集，我们通过全脑nf - κB-p65转录因子检测证实了这一结果。我们的研究揭示了胎儿缺氧以细胞特异性和性别依赖性的方式对新生儿大脑转录组的重大影响，并提供了可能有助于解释新生儿大脑缺氧缺血敏感表型发展的机制见解。在线版本包含补充材料，可在10.1186/s13578-023-01012-8获得。
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. 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. 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. The online version contains supplementary material available at 10.1186/s13578-023-01012-8.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
1.5
作者：
Chen VS;Morrison JP;Southwell MF;Foley JF;Bolon B;Elmore SA
通讯作者：
Elmore SA
影响因子：
5.5
作者：
Bennet, L.;Roelfsema, V.;Gunn, A. J.
通讯作者：
Gunn, A. J.
影响因子：
2.5
作者：
Azevedo, Frederico A. C.;Carvalho, Ludmila R. B.;Herculano-Houzel, Suzana
通讯作者：
Herculano-Houzel, Suzana
影响因子：
15.1
作者：
Diz-Chaves, Yolanda;Astiz, Mariana;Garcia-Segura, Luis M.
通讯作者：
Garcia-Segura, Luis M.