Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson's disease.
Towards physiologically relevant human pluripotent stem cell (hPSC) models of Parkinson's disease.
复制标题
帕金森氏病的生理相关的人类多能干细胞(HPSC)模型。
DOI：
10.1186/s13287-021-02326-5
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发表时间：
2021-04-29
影响因子：
7.5
通讯作者：
Ahfeldt T
中科院分区：
文献类型：
--
作者：
Coccia E;Ahfeldt T
人类胚胎干细胞的衍生、诱导多能干细胞的发现以及基因组编辑方法的飞跃不断激发了人们对帕金森病（PD）等神经退行性疾病新模型开发的热情。 PD 的特征是黑质致密部 (SNpc) 特定区域的多巴胺能神经元 (DN) 相对选择性丧失。虽然晚期退化可能很普遍，但这些独特脆弱的神经元存在刻板的早期退化。人们已经对选择性脆弱性的各种原因进行了调查，但仍有很多不清楚的地方。大多数研究都试图识别最脆弱神经元的细胞自主特性。然而，遗传研究和模型系统的最新发现增加了我们对非细胞自主贡献的理解，包括与星形胶质细胞、驻留或损伤激活的小胶质细胞的区域特异性神经免疫相互作用、神经胶质细胞代谢相互作用、内皮细胞的参与以及对血管系统的损伤。所有这些都会导致特定的脆弱性，并且与衰老和环境因素一起，可能会整合到神经退行性复杂的压力源阈值模型中。在这篇前瞻性综述中，我们综合了使用人类多能干细胞进行帕金森病建模领域的最新进展，重点是黑质纹状体生态位的类器官和复杂共培养模型，以及新兴的 CRISPR 应用来编辑或扰乱帕金森病致病基因和相关风险因素（例如 GBA）的表达，以了解这些基因对相关表型的影响。
The derivation of human embryonic stem cells followed by the discovery of induced pluripotent stem cells and leaps in genome editing approaches have continuously fueled enthusiasm for the development of new models of neurodegenerative diseases such as Parkinson’s disease (PD). PD is characterized by the relative selective loss of dopaminergic neurons (DNs) in specific areas of substantia nigra pars compacta (SNpc). While degeneration in late stages can be widespread, there is stereotypic early degeneration of these uniquely vulnerable neurons. Various causes of selective vulnerability have been investigated but much remains unclear. Most studies have sought to identify cell autonomous properties of the most vulnerable neurons. However, recent findings from genetic studies and model systems have added to our understanding of non-cell autonomous contributions including regional-specific neuro-immune interactions with astrocytes, resident or damage-activated microglia, neuro-glia cell metabolic interactions, involvement of endothelial cells, and damage to the vascular system. All of these contribute to specific vulnerability and, along with aging and environmental factors, might be integrated in a complex stressor-threshold model of neurodegeneration. In this forward-looking review, we synthesize recent advances in the field of PD modeling using human pluripotent stem cells, with an emphasis on organoid and complex co-culture models of the nigrostriatal niche, with emerging CRISPR applications to edit or perturb expression of causal PD genes and associated risk factors, such as GBA, to understand the impact of these genes on relevant phenotypes.
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影响因子：
2.3
作者：
Biegstraaten, M.;van Schaik, I. N.;Hollak, C. E. M.
通讯作者：
Hollak, C. E. M.
DOI：
10.1002/mds.27296
发表时间：
2018-05
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Creed RB;Goldberg MS
通讯作者：
Goldberg MS
影响因子：
56.9
作者：
BEUTLER, E
通讯作者：
BEUTLER, E
影响因子：
82.9
作者：
Blanchard JW;Bula M;Davila-Velderrain J;Akay LA;Zhu L;Frank A;Victor MB;Bonner JM;Mathys H;Lin YT;Ko T;Bennett DA;Cam HP;Kellis M;Tsai LH
通讯作者：
Tsai LH
影响因子：
14.5
作者：
Blauwendraat, Cornelis;Reed, Xylena;Singleton, Andrew B.
通讯作者：
Singleton, Andrew B.