Division of Animal Sciences, University of Missouri, Columbia, MO 65211, USA.
MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO 65211, USA.
Cells. 2024 Jan 24;13(3):215. doi: 10.3390/cells13030215.
Caveolin-1 () is a major plasma membrane protein that plays important functions in cellular metabolism, proliferation, and senescence. Mice lacking show abnormal gene expression in the fetal brain. Though evidence for placental influence on brain development is emerging, whether the ablation of 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 -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 ablation in mice. Interestingly, specific genes related to brain development and neurogenesis were significantly differentially expressed in trophoblast cells due to deletion. Comparison of single-cell gene expression between the placenta and the fetal brain further showed that specific genes such as plexin A1 (), phosphatase and actin regulator 1 () and amyloid precursor-like protein 2 () 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 . The deconvolution of reference cell types from the bulk RNA-seq data further showed that the loss of 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 causes deregulated gene expression in specific cell types of the placenta and the fetal brain in mice.
窖蛋白-1（）是一种主要的质膜蛋白，在细胞代谢、增殖和衰老中发挥重要作用。缺乏的小鼠在胎儿大脑中表现出异常的基因表达。尽管胎盘对大脑发育的影响证据正在出现，但缺失是否会影响大脑-胎盘轴的调节仍未被检验。本研究检验了这样一个假设，即胎盘和胎儿大脑特定细胞中的基因表达变化与-缺失小鼠中大脑-胎盘轴的失调有关。通过进行单细胞 RNA 测序（snRNA-seq）分析，我们表明，由于在小鼠中缺失，滋养外胚层（EVT）和基质细胞的丰度显著受到影响，而细胞滋养层（CTB）或合胞滋养层（STB）则没有受到影响。有趣的是，由于缺失，与大脑发育和神经发生相关的特定基因在滋养细胞中表达显著差异。对胎盘和胎儿大脑单细胞基因表达的比较进一步表明，特定基因如多配体聚糖 A1（）、磷酸酶和肌动蛋白调节因子 1（）和淀粉样前体样蛋白 2（）在胎盘的 EVT 和 STB 细胞之间以及在胎儿大脑的放射状胶质细胞和室管膜细胞之间表达差异。对整个胎盘和胎儿大脑的 bulk RNA-seq 分析进一步鉴定了由于缺失而以相似方式在胎盘和胎儿大脑之间表达差异的基因。从 bulk RNA-seq 数据中推断参考细胞类型进一步表明，缺失对胎盘 EVT 细胞相对于基质细胞的丰度以及胎儿大脑中神经胶质细胞相对于神经元细胞的丰度产生了影响。总之，本研究结果表明，在小鼠中缺失导致胎盘和胎儿大脑特定细胞类型中的基因表达失调。
