School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada.
Sci Rep. 2023 Apr 25;13(1):6763. doi: 10.1038/s41598-023-33869-7.
PTEN hamartoma tumour syndrome is characterised by mutations in the human PTEN gene. We performed transcriptomic and proteomic analyses of neural tissues and primary cultures from heterozygous and homozygous Pten-knockout mice. The somatosensory cortex of heterozygous Pten-knockout mice was enriched in immune response and oligodendrocyte development Gene Ontology (GO) terms. Parallel proteomic analysis revealed differentially expressed proteins (DEPs) related to dendritic spine development, keratinisation and hamartoma signatures. However, primary astrocytes (ASTs) from heterozygous Pten-knockout mice were enriched in the extracellular matrix GO term, while primary cortical neurons (PCNs) were enriched in immediate-early genes. In ASTs from homozygous Pten-knockout mice, cilium-related activity was enriched, while PCNs exhibited downregulation of forebrain neuron generation and differentiation, implying an altered excitatory/inhibitory balance. By integrating DEPs with pre-filtered differentially expressed genes, we identified the enrichment of traits of intelligence, cognitive function and schizophrenia, while DEPs in ASTs were significantly associated with intelligence and depression.
PTEN 错构瘤肿瘤综合征的特征是人类 PTEN 基因突变。我们对杂合子和纯合子 Pten 基因敲除小鼠的神经组织和原代培养物进行了转录组和蛋白质组分析。杂合子 Pten 基因敲除小鼠的体感皮层富含免疫反应和少突胶质细胞发育的基因本体论 (GO) 术语。平行蛋白质组学分析揭示了与树突棘发育、角质化和错构瘤特征相关的差异表达蛋白 (DEP)。然而，杂合子 Pten 基因敲除小鼠的原代星形胶质细胞 (AST) 富含细胞外基质 GO 术语，而原代皮质神经元 (PCN) 富含即刻早期基因。在纯合子 Pten 基因敲除小鼠的 AST 中，纤毛相关活性富集，而 PCN 表现出前脑神经元生成和分化的下调，暗示兴奋性/抑制性平衡的改变。通过将 DEP 与预过滤的差异表达基因整合，我们确定了智力、认知功能和精神分裂症特征的富集，而 AST 中的 DEP 与智力和抑郁显著相关。
