The Board of Governor's Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Genomics Core Facility, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Cell Rep. 2018 Oct 23;25(4):1081-1096.e6. doi: 10.1016/j.celrep.2018.09.076.
Huntington's disease (HD) is a neurodegenerative disease caused by an expanded CAG repeat in the Huntingtin (HTT) gene. Induced pluripotent stem cell (iPSC) models of HD provide an opportunity to study the mechanisms underlying disease pathology in disease-relevant patient tissues. Murine studies have demonstrated that HTT is intricately involved in corticogenesis. However, the effect of mutant Hungtintin (mtHTT) in human corticogenesis has not yet been thoroughly explored. This examination is critical, due to inherent differences in cortical development and timing between humans and mice. We therefore differentiated HD and non-diseased iPSCs into functional cortical neurons. While HD patient iPSCs can successfully differentiate toward a cortical fate in culture, the resulting neurons display altered transcriptomics, morphological and functional phenotypes indicative of altered corticogenesis in HD.
亨廷顿病（HD）是一种由亨廷顿（HTT）基因中 CAG 重复扩展引起的神经退行性疾病。诱导多能干细胞（iPSC）的 HD 模型为研究疾病相关患者组织中疾病发病机制提供了机会。鼠类研究表明 HTT 与皮质发生密切相关。然而，突变的亨廷顿蛋白（mtHTT）在人类皮质发生中的作用尚未得到充分探索。由于人类和老鼠在皮质发育和时间上存在固有差异，因此这项检查至关重要。我们将 HD 和非疾病 iPSC 分化为功能性皮质神经元。虽然 HD 患者的 iPSC 可以在培养中成功地向皮质命运分化，但产生的神经元表现出转录组学、形态和功能表型的改变，表明 HD 中的皮质发生发生了改变。
