Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are...
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| Format: | Article |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/112100 https://orcid.org/0000-0002-0524-5301 https://orcid.org/0000-0001-5016-0756 |
| _version_ | 1826216971620843520 |
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| author | Lim, Ryan G. Quan, Chris Reyes-Ortiz, Andrea M. Lutz, Sarah E. Kedaigle, Amanda J. Wu, Jie Vatine, Gad D. Stocksdale, Jennifer Casale, Malcolm S. Svendsen, Clive N. Fraenkel, Ernest Agalliu, Dritan Thompson, Leslie M. Wasylenko, Theresa Anne Housman, David E |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lim, Ryan G. Quan, Chris Reyes-Ortiz, Andrea M. Lutz, Sarah E. Kedaigle, Amanda J. Wu, Jie Vatine, Gad D. Stocksdale, Jennifer Casale, Malcolm S. Svendsen, Clive N. Fraenkel, Ernest Agalliu, Dritan Thompson, Leslie M. Wasylenko, Theresa Anne Housman, David E |
| author_sort | Lim, Ryan G. |
| collection | MIT |
| description | Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery. |
| first_indexed | 2024-09-23T16:56:05Z |
| format | Article |
| id | mit-1721.1/112100 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:56:05Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1121002022-10-03T09:15:09Z Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits Lim, Ryan G. Quan, Chris Reyes-Ortiz, Andrea M. Lutz, Sarah E. Kedaigle, Amanda J. Wu, Jie Vatine, Gad D. Stocksdale, Jennifer Casale, Malcolm S. Svendsen, Clive N. Fraenkel, Ernest Agalliu, Dritan Thompson, Leslie M. Wasylenko, Theresa Anne Housman, David E Massachusetts Institute of Technology. Department of Biology Wasylenko, Theresa Anne Housman, David E Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery. American Heart Association (12PRE10410000) American Heart Association (CIRMTG2-01152) National Institutes of Health (U.S.) (NIHNS089076) 2017-10-31T16:08:34Z 2017-10-31T16:08:34Z 2017-05 2017-03 2017-10-19T18:41:18Z Article http://purl.org/eprint/type/JournalArticle 2211-1247 http://hdl.handle.net/1721.1/112100 Lim, Ryan G. et al. “Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits.” Cell Reports 19, 7 (May 2017): 1365–1377 © 2017 The Author(s) https://orcid.org/0000-0002-0524-5301 https://orcid.org/0000-0001-5016-0756 http://dx.doi.org/10.1016/j.celrep.2017.04.021 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Lim, Ryan G. Quan, Chris Reyes-Ortiz, Andrea M. Lutz, Sarah E. Kedaigle, Amanda J. Wu, Jie Vatine, Gad D. Stocksdale, Jennifer Casale, Malcolm S. Svendsen, Clive N. Fraenkel, Ernest Agalliu, Dritan Thompson, Leslie M. Wasylenko, Theresa Anne Housman, David E Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title | Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title_full | Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title_fullStr | Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title_full_unstemmed | Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title_short | Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits |
| title_sort | huntington s disease ipsc derived brain microvascular endothelial cells reveal wnt mediated angiogenic and blood brain barrier deficits |
| url | http://hdl.handle.net/1721.1/112100 https://orcid.org/0000-0002-0524-5301 https://orcid.org/0000-0001-5016-0756 |
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