Representing Diversity in the Dish: Using Patient-Derived in Vitro Models to Recreate the Heterogeneity of Neurological Disease.
Representing Diversity in the Dish: Using Patient-Derived in Vitro Models to Recreate the Heterogeneity of Neurological Disease.
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DOI：
10.3389/fnins.2018.00056
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发表时间：
2018
影响因子：
4.3
通讯作者：
Sattler R
中科院分区：
文献类型：
--
作者：
Ghaffari LT;Starr A;Nelson AT;Sattler R
神经系统疾病，包括阿尔茨海默病(AD)和额颞叶痴呆(FTD)等痴呆症，以及肌萎缩侧索硬化症(ALS)等退行性运动神经元疾病，在全球死亡人数中所占比例越来越大。研究这些异质性疾病需要内源性表达全套遗传和表观遗传因素的模型，这些因素可能会影响家族性和散发性患者的疾病发展。在这里，我们讨论了培养患者来源的神经元和胶质细胞来建立神经退行性疾病模型的两种主要方法：将体细胞重新编程为诱导多能干细胞(IPSCs)，并将其分化为神经元或神经胶质细胞；或直接将(DC)体细胞转化为神经元(INeurons)或神经胶质细胞。这两种模型的不同分化技术导致了各种神经元和神经胶质细胞类型，这些细胞已经成功地显示了各种神经疾病的独特特征。产量、分化长度、基因操作的易用性、细胞特异性标记的表达以及疾病发病机制的重述是决定这些方法如何单独或结合使用以确定疾病机制并在个性化医学项目中为不同的患者群体或特定个人确定治疗方法的决定因素。
Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic cells into neurons (iNeurons) or glial cells. Distinct differentiation techniques for both models result in a variety of neuronal and glial cell types, which have been successful in displaying unique hallmarks of a variety of neurological diseases. Yield, length of differentiation, ease of genetic manipulation, expression of cell-specific markers, and recapitulation of disease pathogenesis are presented as determining factors in how these methods may be used separately or together to ascertain mechanisms of disease and identify therapeutics for distinct patient populations or for specific individuals in personalized medicine projects.
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DOI：
10.1016/j.mcn.2013.07.007
发表时间：
2013-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Burkhardt MF;Martinez FJ;Wright S;Ramos C;Volfson D;Mason M;Garnes J;Dang V;Lievers J;Shoukat-Mumtaz U;Martinez R;Gai H;Blake R;Vaisberg E;Grskovic M;Johnson C;Irion S;Bright J;Cooper B;Nguyen L;Griswold-Prenner I;Javaherian A
通讯作者：
Javaherian A
影响因子：
25
作者：
Blanchard, Joel W.;Eade, Kevin T.;Szucs, Attila;Lo Sardo, Valentina;Tsunemoto, Rachel K.;Williams, Daniel;Sanna, Pietro Paolo;Baldwin, Kristin K.
通讯作者：
Baldwin, Kristin K.
影响因子：
3.6
作者：
Cobb MM;Ravisankar A;Skibinski G;Finkbeiner S
通讯作者：
Finkbeiner S
影响因子：
23.9
作者：
Abernathy DG;Kim WK;McCoy MJ;Lake AM;Ouwenga R;Lee SW;Xing X;Li D;Lee HJ;Heuckeroth RO;Dougherty JD;Wang T;Yoo AS
通讯作者：
Yoo AS
影响因子：
8.8
作者：
Almeida S;Zhang Z;Coppola G;Mao W;Futai K;Karydas A;Geschwind MD;Tartaglia MC;Gao F;Gianni D;Sena-Esteves M;Geschwind DH;Miller BL;Farese RV Jr;Gao FB
通讯作者：
Gao FB