Your browser doesn't support javascript.
loading
Aberrant Development Corrected in Adult-Onset Huntington's Disease iPSC-Derived Neuronal Cultures via WNT Signaling Modulation.
Smith-Geater, Charlene; Hernandez, Sarah J; Lim, Ryan G; Adam, Miriam; Wu, Jie; Stocksdale, Jennifer T; Wassie, Brook T; Gold, Maxwell Philip; Wang, Keona Q; Miramontes, Ricardo; Kopan, Lexi; Orellana, Iliana; Joy, Shona; Kemp, Paul J; Allen, Nicholas D; Fraenkel, Ernest; Thompson, Leslie M.
Afiliação
  • Smith-Geater C; Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92697, USA.
  • Hernandez SJ; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA.
  • Lim RG; Department of Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
  • Adam M; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Wu J; Department of Biological Chemistry, University of California Irvine, Irvine, CA 92617, USA.
  • Stocksdale JT; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA.
  • Wassie BT; LeadCrunch, San Diego, CA 92101, USA.
  • Gold MP; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Wang KQ; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA.
  • Miramontes R; Department of Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
  • Kopan L; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA.
  • Orellana I; Department of Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA.
  • Joy S; Neural Stem Cell Institute, Rensselaer, NY 12144, USA.
  • Kemp PJ; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
  • Allen ND; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
  • Fraenkel E; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
  • Thompson LM; Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92697, USA; Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA; Department of Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, C
Stem Cell Reports ; 14(3): 406-419, 2020 03 10.
Article em En | MEDLINE | ID: mdl-32109367
ABSTRACT
Aberrant neuronal development and the persistence of mitotic cellular populations have been implicated in a multitude of neurological disorders, including Huntington's disease (HD). However, the mechanism underlying this potential pathology remains unclear. We used a modified protocol to differentiate induced pluripotent stem cells (iPSCs) from HD patients and unaffected controls into neuronal cultures enriched for medium spiny neurons, the cell type most affected in HD. We performed single-cell and bulk transcriptomic and epigenomic analyses and demonstrated that a persistent cyclin D1+ neural stem cell (NSC) population is observed selectively in adult-onset HD iPSCs during differentiation. Treatment with a WNT inhibitor abrogates this NSC population while preserving neurons. Taken together, our findings identify a mechanism that may promote aberrant neurodevelopment and adult neurogenesis in adult-onset HD striatal neurons with the potential for therapeutic compensation.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Huntington / Células-Tronco Pluripotentes Induzidas / Via de Sinalização Wnt / Neurônios Tipo de estudo: Guideline / Prognostic_studies Limite: Adult / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Huntington / Células-Tronco Pluripotentes Induzidas / Via de Sinalização Wnt / Neurônios Tipo de estudo: Guideline / Prognostic_studies Limite: Adult / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article