Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing.
Dopamine Neuron Diversity: Recent Advances and Current Challenges in Human Stem Cell Models and Single Cell Sequencing.
复制标题
多巴胺神经元多样性：人类干细胞模型和单细胞测序的最新进展和当前挑战。
DOI：
10.3390/cells10061366
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发表时间：
2021-06-01
期刊：
影响因子：
6
通讯作者：
Storm P
中科院分区：
文献类型：
--
作者：
Fiorenzano A;Sozzi E;Parmar M;Storm P
人中脑多巴胺(DA)神经元是一组异质性细胞，具有共同的神经递质表型，在解剖学上非常接近，但具有不同的功能、对变性的敏感性和轴突神经支配靶点。A9 DA神经元亚型控制运动功能，在帕金森病(PD)中主要退化，而A10神经元基本上不受这种情况的影响，它们的功能障碍与神经精神障碍有关。目前，DA神经元只能根据地形图特征进行可靠的分类，包括中脑的解剖位置和前脑的投射靶点。到目前为止，还没有在全基因组水平上提出系统的分子分类。尽管多年来在胚胎和成年小鼠脑中的科学努力使我们能够更好地了解DA神经元生物学的复杂性，但许多人类特有的生物学现象不适合在动物模型中复制。人类细胞系统的建立与先进的计算单细胞转录学相结合，为破译人类DA神经元成熟和多样化的机制以及将其分子异质性与中脑功能联系起来提供了巨大的希望。人类多能干细胞已成为概括成熟DA神经元亚型的关键分子特征的有用工具。在这里，我们回顾了一些最新的进展，并讨论了目前在使用干细胞来模拟人类DA生物学方面的挑战。我们还描述了单细胞RNA测序如何为推动DA前体规范进入成熟DA神经元亚型的分子程序提供关键见解。利用最先进的方法将导致对干细胞来源的DA神经元及其在疾病建模和再生医学中的使用的更好的理解。
Human midbrain dopamine (DA) neurons are a heterogeneous group of cells that share a common neurotransmitter phenotype and are in close anatomical proximity but display different functions, sensitivity to degeneration, and axonal innervation targets. The A9 DA neuron subtype controls motor function and is primarily degenerated in Parkinson’s disease (PD), whereas A10 neurons are largely unaffected by the condition, and their dysfunction is associated with neuropsychiatric disorders. Currently, DA neurons can only be reliably classified on the basis of topographical features, including anatomical location in the midbrain and projection targets in the forebrain. No systematic molecular classification at the genome-wide level has been proposed to date. Although many years of scientific efforts in embryonic and adult mouse brain have positioned us to better understand the complexity of DA neuron biology, many biological phenomena specific to humans are not amenable to being reproduced in animal models. The establishment of human cell-based systems combined with advanced computational single-cell transcriptomics holds great promise for decoding the mechanisms underlying maturation and diversification of human DA neurons, and linking their molecular heterogeneity to functions in the midbrain. Human pluripotent stem cells have emerged as a useful tool to recapitulate key molecular features of mature DA neuron subtypes. Here, we review some of the most recent advances and discuss the current challenges in using stem cells, to model human DA biology. We also describe how single cell RNA sequencing may provide key insights into the molecular programs driving DA progenitor specification into mature DA neuron subtypes. Exploiting the state-of-the-art approaches will lead to a better understanding of stem cell-derived DA neurons and their use in disease modeling and regenerative medicine.
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影响因子：
23.9
作者：
Cahan P;Cacchiarelli D;Dunn SJ;Hemberg M;de Sousa Lopes SMC;Morris SA;Rackham OJL;Del Sol A;Wells CA
通讯作者：
Wells CA
影响因子：
6.2
作者：
Bonilla, Sonia;Hall, Anita C.;Arenas, Ernest
通讯作者：
Arenas, Ernest
影响因子：
46.9
作者：
Cadwell CR;Palasantza A;Jiang X;Berens P;Deng Q;Yilmaz M;Reimer J;Shen S;Bethge M;Tolias KF;Sandberg R;Tolias AS
通讯作者：
Tolias AS
影响因子：
16.2
作者：
Armand EJ;Li J;Xie F;Luo C;Mukamel EA
通讯作者：
Mukamel EA
DOI：
10.1242/dev.126847
发表时间：
2016-06-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Demers CJ;Soundararajan P;Chennampally P;Cox GA;Briscoe J;Collins SD;Smith RL
通讯作者：
Smith RL