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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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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