Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells

Abstract 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...

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Main Authors: Marjolein Heymans, Ricardo Figueiredo, Lucie Dehouck, David Francisco, Yasuteru Sano, Fumitaka Shimizu, Takashi Kanda, Rémy Bruggmann, Britta Engelhardt, Peter Winter, Fabien Gosselet, Maxime Culot
Format: Article
Language:English
Published: BMC 2020-07-01
Series:Fluids and Barriers of the CNS
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12987-020-00208-1
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spelling doaj-55e1fbd5ebc84630ac0ce3c232be8cdb2020-11-25T03:31:58ZengBMCFluids and Barriers of the CNS2045-81182020-07-0117112810.1186/s12987-020-00208-1Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cellsMarjolein Heymans0Ricardo Figueiredo1Lucie Dehouck2David Francisco3Yasuteru Sano4Fumitaka Shimizu5Takashi Kanda6Rémy Bruggmann7Britta Engelhardt8Peter Winter9Fabien Gosselet10Maxime Culot11Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Univ. Artois, UR 2465GenXPro GmbHLaboratoire de la Barrière Hémato-Encéphalique (LBHE), Univ. Artois, UR 2465Interfaculty Bioinformatics Unit and Swiss, Institute of Bioinformatics, University of BernDepartment of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi UniversityDepartment of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi UniversityDepartment of Neurology and Clinical Neuroscience, Graduate School of Medicine, Yamaguchi UniversityInterfaculty Bioinformatics Unit and Swiss, Institute of Bioinformatics, University of BernTheodor Kocher Institute, University of BernGenXPro GmbHLaboratoire de la Barrière Hémato-Encéphalique (LBHE), Univ. Artois, UR 2465Laboratoire de la Barrière Hémato-Encéphalique (LBHE), Univ. Artois, UR 2465Abstract 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.http://link.springer.com/article/10.1186/s12987-020-00208-1Blood–brain barrier1Transcriptome2BBB formation3In vitro4Central nervous system5Brain endothelial cells6
collection DOAJ
language English
format Article
sources DOAJ
author Marjolein Heymans
Ricardo Figueiredo
Lucie Dehouck
David Francisco
Yasuteru Sano
Fumitaka Shimizu
Takashi Kanda
Rémy Bruggmann
Britta Engelhardt
Peter Winter
Fabien Gosselet
Maxime Culot
spellingShingle Marjolein Heymans
Ricardo Figueiredo
Lucie Dehouck
David Francisco
Yasuteru Sano
Fumitaka Shimizu
Takashi Kanda
Rémy Bruggmann
Britta Engelhardt
Peter Winter
Fabien Gosselet
Maxime Culot
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
Blood–brain barrier1
Transcriptome2
BBB formation3
In vitro4
Central nervous system5
Brain endothelial cells6
author_facet Marjolein Heymans
Ricardo Figueiredo
Lucie Dehouck
David Francisco
Yasuteru Sano
Fumitaka Shimizu
Takashi Kanda
Rémy Bruggmann
Britta Engelhardt
Peter Winter
Fabien Gosselet
Maxime Culot
author_sort Marjolein Heymans
title Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
title_short Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
title_full Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
title_fullStr Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
title_full_unstemmed Contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
title_sort contribution of brain pericytes in blood–brain barrier formation and maintenance: a transcriptomic study of cocultured human endothelial cells derived from hematopoietic stem cells
publisher BMC
series Fluids and Barriers of the CNS
issn 2045-8118
publishDate 2020-07-01
description Abstract 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.
topic Blood–brain barrier1
Transcriptome2
BBB formation3
In vitro4
Central nervous system5
Brain endothelial cells6
url http://link.springer.com/article/10.1186/s12987-020-00208-1
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