Stem Cell-Based Organoid Models of Neurodevelopmental Disorders.
Stem Cell-Based Organoid Models of Neurodevelopmental Disorders.
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DOI：
10.1016/j.biopsych.2023.01.012
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发表时间：
2023-04-01
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在过去的十年里，神经发育障碍（NDD）的遗传原因的鉴定出现了爆炸式增长，包括孟德尔，从头和体细胞因素。这些发现为理解细胞和分子机制以及潜在的基因-基因和基因-环境相互作用提供了机会，以支持新的治疗方法。基于干细胞的模型，特别是人脑类器官，可以在人类基因组的背景下捕获疾病相关的等位基因，经工程改造以反映细胞复杂性和发育时间的疾病相关方面。这些模型为NDD带来了关键的见解，如小头畸形，自闭症和局灶性癫痫。但是，内在的类器官与类器官的变异性，某些脑驻留细胞类型的低水平，以及达到成熟所需的长时间培养可能会阻碍进展。最近的几项进展将特定的形态梯度，不同脑细胞类型的混合物和类器官移植到动物模型中。与非人类灵长类类器官的比较一起，人类NDD的机制正在出现。
The last decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders (NDDs), including Mendelian, de novo, and somatic, factors. These discoveries provide opportunities to understand cellular and molecular mechanisms as well as potential gene-gene and gene-environment interactions, to support novel therapies. Stem cell-based models, particularly human brain organoids, can capture disease-associated alleles in the context of the human genome, engineered to mirror disease-relevant aspects of cellular complexity and developmental timing. These models have brought key insights into NDDs as diverse as microcephaly, autism, and focal epilepsy. But intrinsic organoid-to-organoid variability, low levels of certain brain-resident cell types, and long culture times required to reach maturity can impede progress. Several recent advances incorporate specific morphogen gradients, mixtures of diverse brain cell types, and organoid engraftment into animal models. Together with non-human primate organoid comparisons, mechanisms of human NDDs are emerging.
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影响因子：
64.5
作者：
Andersen J;Revah O;Miura Y;Thom N;Amin ND;Kelley KW;Singh M;Chen X;Thete MV;Walczak EM;Vogel H;Fan HC;Paşca SP
通讯作者：
Paşca SP
影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
16.6
作者：
Catlett TS;Onesto MM;McCann AJ;Rempel SK;Glass J;Franz DN;Gómez TM
通讯作者：
Gómez TM
影响因子：
6
作者：
Dooves S;van Velthoven AJH;Suciati LG;Heine VM
通讯作者：
Heine VM
影响因子：
3.6
作者：
Dhaliwal N;Choi WWY;Muffat J;Li Y
通讯作者：
Li Y