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Publication : Integrative multi-omic profiling of adult mouse brain endothelial cells and potential implications in Alzheimer's disease.

First Author  Yu M Year  2023
Journal  Cell Rep Volume  42
Issue  11 Pages  113392
PubMed ID  37925638 Mgi Jnum  J:348166
Mgi Id  MGI:7561383 Doi  10.1016/j.celrep.2023.113392
Citation  Yu M, et al. (2023) Integrative multi-omic profiling of adult mouse brain endothelial cells and potential implications in Alzheimer's disease. Cell Rep 42(11):113392
abstractText  The blood-brain barrier (BBB) is primarily manifested by a variety of physiological properties of brain endothelial cells (ECs), but the molecular foundation for these properties remains incompletely clear. Here, we generate a comprehensive molecular atlas of adult brain ECs using acutely purified mouse ECs and integrated multi-omics. Using RNA sequencing (RNA-seq) and proteomics, we identify the transcripts and proteins selectively enriched in brain ECs and demonstrate that they are partially correlated. Using single-cell RNA-seq, we dissect the molecular basis of functional heterogeneity of brain ECs. Using integrative epigenomics and transcriptomics, we determine that TCF/LEF, SOX, and ETS families are top-ranked transcription factors regulating the BBB. We then validate the identified brain-EC-enriched proteins and transcription factors in normal mouse and human brain tissue and assess their expression changes in mice with Alzheimer's disease. Overall, we present a valuable resource with broad implications for regulation of the BBB and treatment of neurological disorders.
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