Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits
Open accessAbstract
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.
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Together, these reports support the use of iPSCs to generate clinically relevant models of diseased human BBB.
“Together, these reports support the use of iPSCs to generate clinically relevant models of diseased human BBB.”
From Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier (2017) · cites this paper as Lim et al., 2017
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- Authors
- Lim, R. G., Quan, C., Reyes-Ortiz, A. M., Lutz, S. E., Kedaigle, A. J., Gipson, T. A., Wu, J., Vatine, G. D., Stocksdale, J., Casale, M. S., Svendsen, C. N., Fraenkel, E., Housman, D. E., Agalliu, D., & Thompson, L. M.
- Affiliations
- University of California, Irvine (US)
- California State University System (US)
- Columbia University Irving Medical Center (US)
- Massachusetts Institute of Technology (US)
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Agalliu, Dritan
- Thompson, Leslie M.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 19
- Issue
- 7
- Pages
- 1365-1377
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5646270
- OpenAlex
- W2614810773
- Cited by
- 253
- References
- 8
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 14 · 2023: 18 · 2022: 41 · 2021: 36 · 2020: 42 · 2019: 30 · 2018: 22 · 2017: 12
- FWCI
- 14.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Columbia Academic Commons (Columbia University)
- Funders
- American Heart Association (12PRE10410000)
- CIRM (TG2-01152)
- NIH (5F31NS090859-02, NS078370, NS089076, HL116995-01, MH109987)
- NRSA
- NeuroLINCS Center (U54 NS091046)
- NIH Biotechnology Training Program Fellowship (T32GM008334)
- The Leducq Foundation (FDNLEDQ 15CVD 02)
- John Castle to the CUMC Neurology
- Stroke Division
- CIRM Bridges Program (TB1-01182)
- National Science Foundation (DB1-0821391)
- University of California, Irvine (CA-62203)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- Huntington's disease, brain microvascular endothelial cells, blood-brain barrier dysfunction, angiogenesis, Wnt signaling, iPSC-derived endothelial cells, disease modeling, gene expression profiling, drug delivery
- MeSH terms
- Blood-Brain Barrier, Humans, Huntington Disease, Neovascularization, Physiologic, Endothelial Cells, beta Catenin, Gene Regulatory Networks, Microvessels, Induced Pluripotent Stem Cells, Transcytosis, Transcriptome, Wnt Signaling Pathway
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