Aberrant Development Corrected in Adult-Onset Huntington's Disease iPSC-Derived Neuronal Cultures via WNT Signaling Modulation
作者: Charlene Smith-GeaterSarah J. HernandezRyan G. LimMiriam AdamJie WuJennifer T. StocksdaleBrook T. WassieMaxwell Philip GoldKeona Q. WangRicardo MiramontesLexi KopanIliana OrellanaShona JoyPaul J. KempNicholas D. AllenErnest FraenkelLeslie M. Thompson
作者单位: 1Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA 92697, USA
2Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 96267, USA
3Department of Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697, USA
4Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
5Department of Biological Chemistry, University of California Irvine, Irvine, CA 92617, USA
6LeadCrunch, San Diego, CA 92101, USA
7Neural Stem Cell Institute, Rensselaer, NY 12144, USA
8School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
刊名: Stem Cell Reports, 2020, Vol.14 (3), pp.406-419
来源数据库: Elsevier Journal
DOI: 10.1016/j.stemcr.2020.01.015
关键词: Huntington's diseaseMedium spiny neuronsWNT signalingNeural stem cellsAdult-onset HDInduced pluripotent stem cellsSingle-cell RNA-seqDevelopmentCell cycle
原始语种摘要: Summary(#br)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...
全文获取路径: Elsevier  (合作)

  • unaffected 末触动的
  • adult 成体
  • potential 
  • neurogenesis 神经发生
  • differentiate 微分
  • pluripotent 多能的
  • mitotic 有丝分裂的
  • striatal 纹状体的
  • cyclin 细胞周期蛋白
  • population 母体