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


ABSTRACT: 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.

SUBMITTER: Yu M 

PROVIDER: S-EPMC10843806 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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

Yu Min M   Nie Yage Y   Yang Jiawen J   Yang Shilun S   Li Rui R   Rao Varsha V   Hu Xiaoyan X   Fang Cheng C   Li Simeng S   Song Dengpan D   Guo Fuyou F   Snyder Michael P MP   Chang Howard Y HY   Kuo Calvin J CJ   Xu Jin J   Chang Junlei J  

Cell reports 20231104 11


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 c  ...[more]

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