Role of caveolin-1 in metabolic programming of fetal brain

Islam, Maliha; Behura, Susanta K.

doi:10.1016/j.isci.2023.107710

Cited by 3 publications

(12 citation statements)

References 134 publications

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“…These results suggested that the genes related to a combination of developmental and aging processes and the regulation of alternative splicing processes were tightly controlled during fetal brain development. While AKR/J mice show the ecotropic expression of endogenous retroviral genes (AK virus) [59], Cav1-null mice show metabolic and cellular abnormalities in the fetal brain [27]. Despite these developmental abnormalities, Cav1-null mice are not embryonic-lethal, suggesting that these mice might have developed adaptive mechanisms to counter these early-life developmental abnormalities.…”

Section: Discussionmentioning

confidence: 99%

“…The vaginal plug was observed to keep a record of the start of pregnancy (day 1). On days (d) 12, 15, and 17, the pregnant mice were euthanized, the fetuses were collected [15] and washed in sterile PBS, and the whole brain was dissected from each fetus [27].…”

Section: Animals and Sample Collectionmentioning

confidence: 99%

“…The quality reads were then mapped to the mouse reference genome GRCm39 using the STAR aligner [43]. The read count data were analyzed using edgeR [44] to determine the significance of the differential expression, as described in our earlier works [27,45,46]. The read count and raw data were submitted to the Gene Expression Omnibus or GEO database (accession number GSE252079).…”

Section: Rna-seq Data Analysismentioning

confidence: 99%

“…Mice lacking the Cav1 gene show impaired endothelia function [26]. The ablation of Cav1 alters the metabolic regulation of the fetal brain [27] and reduce mouse longevity by nearly 50% [28]. Cav1-null mice, though viable and fertile, show hyperproliferative and vascular abnormalities [29].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

Islam,

Behura

2024

Genes

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The objective of this study was to investigate gene regulation of the developing fetal brain from congenic or inbred mice strains that differed in longevity. Gene expression and alternative splice variants were analyzed in a genome-wide manner in the fetal brain of C57BL/6J mice (long-lived) in comparison to B6.Cg-Cav1tm1Mls/J (congenic, short-lived) and AKR/J (inbred, short-lived) mice on day(d) 12, 15, and 17 of gestation. The analysis showed a contrasting gene expression pattern during fetal brain development in these mice. Genes related to brain development, aging, and the regulation of alternative splicing were significantly differentially regulated in the fetal brain of the short-lived compared to long-lived mice during development from d15 and d17. A significantly reduced number of splice variants was observed on d15 compared to d12 or d17 in a strain-dependent manner. An epigenetic clock analysis of d15 fetal brain identified DNA methylations that were significantly associated with single-nucleotide polymorphic sites between AKR/J and C57BL/6J strains. These methylations were associated with genes that show epigenetic changes in an age-correlated manner in mice. Together, the finding of this study suggest that fetal brain development and longevity are epigenetically linked, supporting the emerging concept of the early-life origin of longevity.

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Section: Discussionmentioning

confidence: 99%

Section: Animals and Sample Collectionmentioning

confidence: 99%

Section: Rna-seq Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

Islam,

Behura

2024

Genes

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“…Recently, we showed that the ablation of Caveolin-1 (Cav1), a key regulator of cell metabolism, proliferation and senescence, was associated with metabolic programming of the brain in mice [17]. By performing single-nuclei RNA sequencing (snRNA-seq), the same study [17] further showed that specific cell types of the fetal brain were deregulated due to the ablation of Cav1.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptional Response of the Placenta to the Ablation of Caveolin-1: Insights into the Adaptive Regulation of Brain–Placental Axis in Mice

Islam,

Behura

2024

Cells

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Caveolin-1 (Cav1) is a major plasma membrane protein that plays important functions in cellular metabolism, proliferation, and senescence. Mice lacking Cav1 show abnormal gene expression in the fetal brain. Though evidence for placental influence on brain development is emerging, whether the ablation of Cav1 affects the regulation of the brain–placental axis remains unexamined. The current study tests the hypothesis that gene expression changes in specific cells of the placenta and the fetal brain are linked to the deregulation of the brain–placental axis in Cav1-null mice. By performing single-nuclei RNA sequencing (snRNA-seq) analyses, we show that the abundance of the extravillious trophoblast (EVT) and stromal cells, but not the cytotrophoblast (CTB) or syncytiotrophoblast (STB), are significantly impacted due to Cav1 ablation in mice. Interestingly, specific genes related to brain development and neurogenesis were significantly differentially expressed in trophoblast cells due to Cav1 deletion. Comparison of single-cell gene expression between the placenta and the fetal brain further showed that specific genes such as plexin A1 (Plxna1), phosphatase and actin regulator 1 (Phactr1) and amyloid precursor-like protein 2 (Aplp2) were differentially expressed between the EVT and STB cells of the placenta, and also, between the radial glia and ependymal cells of the fetal brain. Bulk RNA-seq analysis of the whole placenta and the fetal brain further identified genes differentially expressed in a similar manner between the placenta and the fetal brain due to the absence of Cav1. The deconvolution of reference cell types from the bulk RNA-seq data further showed that the loss of Cav1 impacted the abundance of EVT cells relative to the stromal cells in the placenta, and that of the glia cells relative to the neuronal cells in the fetal brain. Together, the results of this study suggest that the ablation of Cav1 causes deregulated gene expression in specific cell types of the placenta and the fetal brain in mice.

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Relevance of the regulation of the brain-placental axis to the nocturnal bottleneck of mammals

Poudel,

Behura

2024

Placenta

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Role of caveolin-1 in metabolic programming of fetal brain

Cited by 3 publications

References 134 publications

Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

Molecular Regulation of Fetal Brain Development in Inbred and Congenic Mouse Strains Differing in Longevity

Single-Cell Transcriptional Response of the Placenta to the Ablation of Caveolin-1: Insights into the Adaptive Regulation of Brain–Placental Axis in Mice

Relevance of the regulation of the brain-placental axis to the nocturnal bottleneck of mammals

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