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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; Gipson, Theresa A; Wu, Jie; Vatine, Gad D; Stocksdale, Jennifer; Casale, Malcolm S; Svendsen, Clive N; Fraenkel, Ernest; Housman, David E; Agalliu, Dritan; Thompson, Leslie M.
Afiliación
  • Lim RG; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; UCI MIND, University of California, Irvine, Irvine, CA 92697, USA.
  • Quan C; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA; Department of Biological Sciences, California State University, Long Beach, 1250 Bellflower Boulevard, Long Beach, CA 90840, USA.
  • Reyes-Ortiz AM; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
  • Lutz SE; Departments of Neurology, Pathology, and Cell Biology and Pharmacology, Columbia University Medical Center, New York, NY 10032, USA.
  • Kedaigle AJ; Computational and Systems Biology Graduate Program, MIT, Cambridge, MA 02139, USA.
  • Gipson TA; Center for Cancer Research, MIT, Cambridge, MA 02139, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Wu J; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
  • Vatine GD; Department of Biomedical Sciences, The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Stocksdale J; UCI MIND, University of California, Irvine, Irvine, CA 92697, USA.
  • Casale MS; Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA.
  • Svendsen CN; Department of Biomedical Sciences, The Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Fraenkel E; Department of Biological Engineering, MIT, Cambridge, MA 02139, USA.
  • Housman DE; Center for Cancer Research, MIT, Cambridge, MA 02139, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Agalliu D; Departments of Neurology, Pathology, and Cell Biology and Pharmacology, Columbia University Medical Center, New York, NY 10032, USA; Columbia Translational Neuroscience Initiative, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: da191@cumc.columbia.edu.
  • Thompson LM; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA; UCI MIND, University of California, Irvine, Irvine, CA 92697, USA; Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA; Psychiatry and Human Behavior, University of California,
Cell Rep ; 19(7): 1365-1377, 2017 05 16.
Article en En | MEDLINE | ID: mdl-28514657
ABSTRACT
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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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Enfermedad de Huntington / Neovascularización Fisiológica / Células Endoteliales / Microvasos / Células Madre Pluripotentes Inducidas / Vía de Señalización Wnt Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Enfermedad de Huntington / Neovascularización Fisiológica / Células Endoteliales / Microvasos / Células Madre Pluripotentes Inducidas / Vía de Señalización Wnt Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos