A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture
Vascular endothelial cells (ECs) derived from the central nervous system (CNS) variably lose their unique barrier properties during in vitro culture, hindering the development of robust assays for blood-brain barrier (BBB) function, including drug permeability and extrusion assays. In previous work...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/51276 |
| _version_ | 1811201359320449024 |
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| author | Mark F Sabbagh Jeremy Nathans |
| author_facet | Mark F Sabbagh Jeremy Nathans |
| author_sort | Mark F Sabbagh |
| collection | DOAJ |
| description | Vascular endothelial cells (ECs) derived from the central nervous system (CNS) variably lose their unique barrier properties during in vitro culture, hindering the development of robust assays for blood-brain barrier (BBB) function, including drug permeability and extrusion assays. In previous work (Sabbagh et al., 2018) we characterized transcriptional and accessible chromatin landscapes of acutely isolated mouse CNS ECs. In this report, we compare transcriptional and accessible chromatin landscapes of acutely isolated mouse CNS ECs versus mouse CNS ECs in short-term in vitro culture. We observe that standard culture conditions are associated with a rapid and selective loss of BBB transcripts and chromatin features, as well as a greatly reduced level of beta-catenin signaling. Interestingly, forced expression of a stabilized derivative of beta-catenin, which in vivo leads to a partial conversion of non-BBB CNS ECs to a BBB-like state, has little or no effect on gene expression or chromatin accessibility in vitro. |
| first_indexed | 2024-04-12T02:20:33Z |
| format | Article |
| id | doaj.art-dda4cb2fb5b04c3eba54870a3d3c3cf6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:20:33Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-dda4cb2fb5b04c3eba54870a3d3c3cf62022-12-22T03:52:08ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.51276A genome-wide view of the de-differentiation of central nervous system endothelial cells in cultureMark F Sabbagh0https://orcid.org/0000-0003-1996-5251Jeremy Nathans1https://orcid.org/0000-0001-8106-5460Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesVascular endothelial cells (ECs) derived from the central nervous system (CNS) variably lose their unique barrier properties during in vitro culture, hindering the development of robust assays for blood-brain barrier (BBB) function, including drug permeability and extrusion assays. In previous work (Sabbagh et al., 2018) we characterized transcriptional and accessible chromatin landscapes of acutely isolated mouse CNS ECs. In this report, we compare transcriptional and accessible chromatin landscapes of acutely isolated mouse CNS ECs versus mouse CNS ECs in short-term in vitro culture. We observe that standard culture conditions are associated with a rapid and selective loss of BBB transcripts and chromatin features, as well as a greatly reduced level of beta-catenin signaling. Interestingly, forced expression of a stabilized derivative of beta-catenin, which in vivo leads to a partial conversion of non-BBB CNS ECs to a BBB-like state, has little or no effect on gene expression or chromatin accessibility in vitro.https://elifesciences.org/articles/51276blood-brain barrierbeta-cateninchromatinWntcell cultureendothelial |
| spellingShingle | Mark F Sabbagh Jeremy Nathans A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture eLife blood-brain barrier beta-catenin chromatin Wnt cell culture endothelial |
| title | A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture |
| title_full | A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture |
| title_fullStr | A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture |
| title_full_unstemmed | A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture |
| title_short | A genome-wide view of the de-differentiation of central nervous system endothelial cells in culture |
| title_sort | genome wide view of the de differentiation of central nervous system endothelial cells in culture |
| topic | blood-brain barrier beta-catenin chromatin Wnt cell culture endothelial |
| url | https://elifesciences.org/articles/51276 |
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