Integrative multi-omic profiling of adult mouse brain endothelial cells and potential implications in Alzheimer's disease.
Cell Rep
; 42(11): 113392, 2023 11 28.
Article
en En
| MEDLINE
| ID: mdl-37925638
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Endoteliales
/
Enfermedad de Alzheimer
Límite:
Adult
/
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2023
Tipo del documento:
Article
País de afiliación:
China