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鼻中隔培养间充质细胞作为精神分裂症发病机制神经发育成分的细胞模型。

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

机构信息

Department of Cell Biology, State University of New York at Downstate, Brooklyn, NY 11203, USA.

Department of Otolaryngology, State University of New York at Downstate, Brooklyn, NY 11203, USA.

出版信息

Int J Mol Sci. 2023 Oct 19;24(20):15339. doi: 10.3390/ijms242015339.

Abstract

The study of neurodevelopmental molecular mechanisms in schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously utilized cell lines with neural progenitor properties (CNON) derived from the superior or middle turbinates of patients with schizophrenia and control groups to study schizophrenia-specific gene expression. In this study, we analyzed single-cell RNA seq data from two CNON cell lines (one derived from an individual with schizophrenia (SCZ) and the other from a control group) and two biopsy samples from the middle turbinate (MT) (also from an individual with SCZ and a control). We compared our data with previously published data regarding the olfactory neuroepithelium and demonstrated that CNON originated from a single cell type present both in middle turbinate and the olfactory neuroepithelium and expressed in multiple markers of mesenchymal cells. To define the relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data derived from an embryonic brain and found that the expression profile of the CNON closely matched the expression profile one of the cell types in the embryonic brain. Finally, we evaluated the differences between SCZ and control samples to assess the utility and potential benefits of using CNON single-cell RNA seq to study the etiology of schizophrenia.

摘要

精神分裂症神经发育分子机制的研究需要开发适当的生物学模型,如患者来源的细胞及其衍生物。我们之前利用源自精神分裂症患者和对照组的上鼻甲或中鼻甲的具有神经祖细胞特性的细胞系 (CNON) 来研究精神分裂症特异性基因表达。在这项研究中,我们分析了来自两个 CNON 细胞系(一个源自精神分裂症患者 (SCZ),另一个源自对照组)和两个中鼻甲活检样本(也来自 SCZ 患者和对照组)的单细胞 RNA-seq 数据。我们将我们的数据与之前关于嗅神经上皮的已发表数据进行了比较,并表明 CNON 源自中鼻甲和嗅神经上皮中存在的单一细胞类型,并表达多种间充质细胞标志物。为了确定 CNON 与发育中人类大脑的相关性,我们还将 CNON 数据集与源自胚胎大脑的 scRNA-seq 数据进行了比较,发现 CNON 的表达谱与胚胎大脑中一种细胞类型的表达谱非常匹配。最后,我们评估了 SCZ 和对照样本之间的差异,以评估使用 CNON 单细胞 RNA-seq 研究精神分裂症病因的效用和潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a749/10607243/4cf70b9df735/ijms-24-15339-g001.jpg

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