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Single‐cell RNA sequencing analysis for common molecular signatures of microvascular injury
Author(s) -
Guo Xinying,
Zhao Zhen
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047642
Subject(s) - traumatic brain injury , cell , neurodegeneration , cell type , extracellular matrix , rna , biology , computational biology , gene , neuroscience , bioinformatics , medicine , pathology , microbiology and biotechnology , disease , genetics , psychiatry
Background Mild Traumatic brain injury (mTBI) is a significant risk factor for Alzheimer’s disease (AD). Given that microvascular injury is common and persistent following mild TBI and that neurodegeneration is a late consequence following some TBIs, vascular dysfunction may be an important link between mTBI and AD. However, little attention has been focused on how the cerebral vasculature responds following mTBI induced AD. The goal of our work is to evaluate the potential common molecular signatures in cerebral microvessels in conditions such as mTBI, AD affected, and aging using single‐cell RNA sequence (sc‐RNA seq) approach. Method The processed single‐cell gene UMI count information from the study of single‐cell sequencing was collected for the secondary analysis using the newest R Seurat Package. Cell count matrix from different groups were integrated using a new method, which is to identify ‘anchors’ across diverse single cell data types in order to transfer information accurately across experiments. After integration, the vasculature cells are taken for another round of clustering to reveal heterogeneity within the vasculature cell. This subsetting of the data enabled us to highlight more subtle changes within the vasculature cell and uncover the unique change which is masked because of few vessel cells. Result Through analyzing vascular cells from the sc‐RNA seq data of mTBI dataset and aging dataset, we found differential expression genes of endothelial cells from two datasets, and discovered that microvascular injury is related to the damage of extracellular matrix, metabolic crisis, transport barrier dysfunction, protein refolding, blood flow, signaling, and changes of binding between molecules. Conclusion Single cell genomics provides unique information about how mTBI and aging impacts diverse cell types, adding new insights into the pathogenic pathways amenable to therapeutics in mTBI induced late‐onset Alzheimer’s disease. Therapeutic approaches against microvessel injury will have important implications for future treatment of AD and other neurodegenerative diseases.