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Series GSE154901 Query DataSets for GSE154901
Status Public on Jul 23, 2020
Title Non-human primate blood-brain barrier and in vitro brain endothelium: from transcriptome to the establishment of a new model
Organism Macaca fascicularis
Experiment type Expression profiling by high throughput sequencing
Summary The blood-brain barrier (BBB) represents a major challenge when developing central nervous system (CNS)-active therapeutics. The non-human primate (NHP)-brain endothelium constitutes an essential alternative to human in the prediction of molecule trafficking across the BBB and in the search of new brain-specific transport mechanisms. This study presents a comparison between the NHP transcriptome of freshly isolated brain microcapillaries and in vitro-selected brain endothelial cells (BECs), focusing on important BBB features – tight junctions, receptors mediating transcytosis (RMT), ABC and SLC transporters. In vitro BECs conserved most of the BBB key elements for barrier integrity and control of molecular trafficking. We also assessed the function of RMT via the Transferrin Receptor (TFRC) in the characterized NHP-BBB model, where both human transferrin and anti-hTFRC antibody showed increased apical-to-basolateral passage in comparison to control molecules. In parallel, we investigated eventual BBB-related regional differences in 7-day in vitro-selected BECs from 5 brain structures: brainstem, cerebellum, cortex, hippocampus and striatum. Our analysis retrieved very few differences in the brain endothelium from these 5 brain regions, suggesting a rather homogeneous BBB role and function across the brain parenchyma. In conclusion, the presently established NHP-derived BBB model closely mimics the physiological BBB, therefore representing a ready-to-use tool for assessment of the penetration of biotherapeutics into the human CNS.
 
Overall design 7 sample groups:
Isolated brain microvessels_Cortex_P0D0
Brain Endothetlail Cells (BECs)_Cortex_P0D7
Brain Endothetlail Cells (BECs)_Cortex-P1D7
Brain Endothetlail Cells (BECs)_Brainstem_P0D7
Brain Endothetlail Cells (BECs)_Hippocampus_P0D7
Brain Endothetlail Cells (BECs)_Striatum _P0D7
Brain Endothetlail Cells (BECs)_Cerebellum _P0D7
 
Contributor(s) Chaves C, Do T, Cegarra C, Roudières V, Tolou S, Thill G, Rocher C, Didier M, Lesuisse D
Citation(s) 33066641, 36108060
Submission date Jul 22, 2020
Last update date Sep 27, 2022
Contact name Dominique Lesuisse
E-mail(s) dominique.lesuisse@sanofi.com
Phone +33160496857
Organization name Sanofi
Department Rare and neurologic diseases therapeutic area
Lab Tissue Barriers group
Street address 1, avenue Pierre Brossolette
City Chilly-Mazarin
ZIP/Postal code 91385
Country France
 
Platforms (1)
GPL28212 Illumina NovaSeq 6000 (Macaca fascicularis)
Samples (44)
GSM4682313 1_BBB029_J0: Isolated brain microvessels_Cortex_P0D0_rep1
GSM4682314 2_BBB030_J0: Isolated brain microvessels_Cortex_P0D0_rep2
GSM4682315 3_BBB031_J0: Isolated brain microvessels_Cortex_P0D0_rep3
Relations
BioProject PRJNA647856
SRA SRP273072

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE154901_FPKM_DATA_matrix.xlsx 8.6 Mb (ftp)(http) XLSX
GSE154901_Raw_Counts_matrix.xlsx 6.1 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
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