Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis
<p dir="ltr">Angiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. Chemical genetic screening of endothelial tube formation provides a robust approach for identifying signalling components that impact microvascular net...
محفوظ في:
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| مؤلفون آخرون: | |
| منشور في: |
2020
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513512870510592 |
|---|---|
| author | Heba Z. Sailem (3262068) |
| author2 | Ayman Al Haj Zen (16614801) |
| author2_role | author |
| author_facet | Heba Z. Sailem (3262068) Ayman Al Haj Zen (16614801) |
| author_role | author |
| dc.creator.none.fl_str_mv | Heba Z. Sailem (3262068) Ayman Al Haj Zen (16614801) |
| dc.date.none.fl_str_mv | 2020-08-14T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-020-70440-0 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Morphological_landscape_of_endothelial_cell_networks_reveals_a_functional_role_of_glutamate_receptors_in_angiogenesis/25957975 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Neurosciences Oncology and carcinogenesis Angiogenesis Cancer Ischemic vascular disease Alzheimer's disease Gene expression Endothelial tube formation Prognosis |
| dc.title.none.fl_str_mv | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Angiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. Chemical genetic screening of endothelial tube formation provides a robust approach for identifying signalling components that impact microvascular network morphology as well as endothelial cell biology. However, the analysis of the resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 characterised drugs, we found that drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed that a group of glutamate receptor antagonists enhances branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes is associated with the prognosis of Alzheimer’s patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesis-related diseases.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-020-70440-0" target="_blank">https://dx.doi.org/10.1038/s41598-020-70440-0</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_e3adfac1ef6e875999acd9eefdb70f80 |
| identifier_str_mv | 10.1038/s41598-020-70440-0 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25957975 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesisHeba Z. Sailem (3262068)Ayman Al Haj Zen (16614801)Biomedical and clinical sciencesClinical sciencesNeurosciencesOncology and carcinogenesisAngiogenesisCancerIschemic vascular diseaseAlzheimer's diseaseGene expressionEndothelial tube formationPrognosis<p dir="ltr">Angiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. Chemical genetic screening of endothelial tube formation provides a robust approach for identifying signalling components that impact microvascular network morphology as well as endothelial cell biology. However, the analysis of the resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 characterised drugs, we found that drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed that a group of glutamate receptor antagonists enhances branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes is associated with the prognosis of Alzheimer’s patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesis-related diseases.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-020-70440-0" target="_blank">https://dx.doi.org/10.1038/s41598-020-70440-0</a></p>2020-08-14T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-020-70440-0https://figshare.com/articles/journal_contribution/Morphological_landscape_of_endothelial_cell_networks_reveals_a_functional_role_of_glutamate_receptors_in_angiogenesis/25957975CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259579752020-08-14T09:00:00Z |
| spellingShingle | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis Heba Z. Sailem (3262068) Biomedical and clinical sciences Clinical sciences Neurosciences Oncology and carcinogenesis Angiogenesis Cancer Ischemic vascular disease Alzheimer's disease Gene expression Endothelial tube formation Prognosis |
| status_str | publishedVersion |
| title | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| title_full | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| title_fullStr | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| title_full_unstemmed | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| title_short | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| title_sort | Morphological landscape of endothelial cell networks reveals a functional role of glutamate receptors in angiogenesis |
| topic | Biomedical and clinical sciences Clinical sciences Neurosciences Oncology and carcinogenesis Angiogenesis Cancer Ischemic vascular disease Alzheimer's disease Gene expression Endothelial tube formation Prognosis |