Single Cell Transcriptomics of Ependymal Cells Across Age, Region and Species Reveals Cilia-Related and Metal Ion Regulatory Roles as Major Conserved Ependymal Cell Functions.

Single Cell Transcriptomics of Ependymal Cells Across Age, Region and Species Reveals Cilia-Related and Metal Ion Regulatory Roles as Major Conserved Ependymal Cell Functions.
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不同年龄、地区和物种的室管膜细胞的单细胞转录组学揭示了纤毛相关和金属离子调节作用是室管膜细胞的主要保守功能。

DOI:
10.3389/fncel.2021.703951
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发表时间:
2021
影响因子:
5.3
通讯作者:
Stratton JA
Stratton JA
中科院分区:
医学2区
文献类型:
--
作者:
MacDonald A;Lu B;Caron M;Caporicci-Dinucci N;Hatrock D;Petrecca K;Bourque G;Stratton JA

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室管膜细胞是纤毛上皮神经胶质细胞,其从放射状神经胶质沿着脑室和椎管的表面发育。它们在脑脊髓液(CSF)稳态、脑代谢和脑废物清除中起关键作用。这些细胞与整个生命周期的疾病有关,包括发育障碍、癌症和神经退行性疾病。尽管如此,室管膜细胞仍然在很大程度上研究不足。使用从公开数据集中提取的单细胞RNA测序数据,我们在跨年龄,地区和物种的室管膜细胞基因签名的显着保护方面取得了关键发现。通过这种无偏见的分析,我们发现,我们观察到的最具代表性的室管膜细胞功能之一与金属离子稳态中严重不足的作用有关。我们的分析还揭示了不同区域和年龄的神经系统室管膜细胞的不同亚型和状态。例如,新生儿室管膜细胞保持与发育过程一致的基因特征,例如确定左/右对称性;而成年心室室管膜细胞,而不是椎管室管膜细胞,似乎表达参与调节细胞运输和炎症的基因。总之,这些发现突出了室管膜细胞的未被充分认识的功能,这对于研究这些细胞在健康和疾病中的作用非常重要。
Ependymal cells are ciliated-epithelial glial cells that develop from radial glia along the surface of the ventricles of the brain and the spinal canal. They play a critical role in cerebrospinal fluid (CSF) homeostasis, brain metabolism, and the clearance of waste from the brain. These cells have been implicated in disease across the lifespan including developmental disorders, cancer, and neurodegenerative disease. Despite this, ependymal cells remain largely understudied. Using single-cell RNA sequencing data extracted from publicly available datasets, we make key findings regarding the remarkable conservation of ependymal cell gene signatures across age, region, and species. Through this unbiased analysis, we have discovered that one of the most overrepresented ependymal cell functions that we observed relates to a critically understudied role in metal ion homeostasis. Our analysis also revealed distinct subtypes and states of ependymal cells across regions and ages of the nervous system. For example, neonatal ependymal cells maintained a gene signature consistent with developmental processes such as determination of left/right symmetry; while adult ventricular ependymal cells, not spinal canal ependymal cells, appeared to express genes involved in regulating cellular transport and inflammation. Together, these findings highlight underappreciated functions of ependymal cells, which will be important to investigate in order to better understand these cells in health and disease.
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