Heymans, Marjolein; Figueiredo, Ricardo; Dehouck, Lucie; Francisco, David; Sano, Yasuteru; Shimizu, Fumitaka; Kanda, Takashi; Bruggmann, Rémy; Engelhardt, Britta; Winter, Peter; Gosselet, Fabien; Culot, Maxime (2020). Contribution of brain pericytes in blood-brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells. Fluids and barriers of the CNS, 17(1), p. 48. BioMed Central 10.1186/s12987-020-00208-1
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Formation, maintenance, and repair of the blood-brain barrier (BBB) are critical for central nervous system homeostasis. The interaction of endothelial cells (ECs) with brain pericytes is known to induce BBB characteristics in brain ECs during embryogenesis and can be used to differentiate human ECs from stem cell source in in vitro BBB models. However, the molecular events involved in BBB maturation are not fully understood. To this end, human ECs derived from hematopoietic stem cells were cultivated with either primary bovine or cell line-derived human brain pericytes to induce BBB formation. Subsequently, the transcriptomic profiles of solocultured vs. cocultured ECs were analysed over time by Massive Analysis of cDNA Ends (MACE) technology. This RNA sequencing method is a 3'-end targeted, tag-based, reduced representation transcriptome profiling technique, that can reliably quantify all polyadenylated transcripts including those with low expression. By analysing the generated transcriptomic profiles, we can explore the molecular processes responsible for the functional changes observed in ECs in coculture with brain pericytes (e.g. barrier tightening, changes in the expression of transporters and receptors). Our results identified several up- and downregulated genes and signaling pathways that provide a valuable data source to further delineate complex molecular processes that are involved in BBB formation and BBB maintenance. In addition, this data provides a source to identify novel targets for central nervous system drug delivery strategies.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Ferreira Francisco, David Miguel, Bruggmann, Rémy, Engelhardt, Britta |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2045-8118 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Ursula Zingg-Zünd |
Date Deposited: |
21 Jan 2021 08:18 |
Last Modified: |
05 Dec 2022 15:44 |
Publisher DOI: |
10.1186/s12987-020-00208-1 |
PubMed ID: |
32723387 |
Uncontrolled Keywords: |
BBB formation3 Blood–brain barrier1 Brain endothelial cells6 Brain pericytes8 Central nervous system5 Human hematopoietic stem cells7 In vitro4 Transcriptome2 |
BORIS DOI: |
10.48350/150905 |
URI: |
https://boris.unibe.ch/id/eprint/150905 |
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