脆性X综合征
神经科学
FMR1型
诱导多能干细胞
生物
背景(考古学)
表型
神经干细胞
干细胞
细胞生物学
胚胎干细胞
脆性x
遗传学
古生物学
基因
作者
Marine Krzisch,Hao Wu,Bingbing Yuan,Troy W. Whitfield,X. Shawn Liu,Dongdong Fu,Carrie Garrett-Engele,Andrew S. Khalil,Tenzin Lungjangwa,Jennifer Shih,Aaron N. Chang,Stephen T. Warren,Angela Cacace,Kristin Andrykovich,Rosalie Rietjens,Owen B. Wallace,Mriganka Sur,Bhav Jain,Rudolf Jaenisch
标识
DOI:10.1016/j.biopsych.2022.08.020
摘要
Fragile X syndrome (FXS) is characterized by physical abnormalities, anxiety, intellectual disability, hyperactivity, autistic behaviors, and seizures. Abnormal neuronal development in FXS is poorly understood. Data on patients with FXS remain scarce, and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons.To mimic human neuron development in vivo, we coinjected neural precursor cells derived from FXS patient-derived induced pluripotent stem cells and neural precursor cells derived from corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice.The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Immunofluorescence and single and bulk RNA sequencing analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, we found increased percentages of Arc- and Egr-1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons.This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3-dimensional context.
科研通智能强力驱动
Strongly Powered by AbleSci AI