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人多能干细胞向内侧神经节隆起细胞与尾侧神经节隆起细胞的分化。

Differentiation of human pluripotent stem cells into Medial Ganglionic Eminence vs. Caudal Ganglionic Eminence cells.

作者信息

Ahn Sandra, Kim Tae-Gon, Kim Kwang-Soo, Chung Sangmi

机构信息

Translational Stem Cell Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.

Molecular Neurobiology Laboratory, Department of Psychiatry and Program in Neuroscience, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA.

出版信息

Methods. 2016 May 15;101:103-12. doi: 10.1016/j.ymeth.2015.09.009. Epub 2015 Sep 10.

DOI:10.1016/j.ymeth.2015.09.009
PMID:26364591
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4786472/
Abstract

Human pluripotent stem cells (PSCs) represent an opportunity to study human development in vitro, to model diseases in a dish, to screen drugs as well as to provide an unlimited and ethically unimpeded source of therapeutic cells. Cortical GABAergic interneurons, which are generated from Medial Ganglionic Eminence (MGE) cells and Caudal Ganglionic Eminence (CGE) cells during embryonic development, regulate cortical neural networks by providing inhibitory inputs. Their malfunction, resulting in failure to intricately regulate neural circuit balance, has been implicated in brain diseases, such as schizophrenia, autism and epilepsy. In this study, using combinatorial and temporal modulation of developmentally relevant dorsoventral and rostrocaudal signaling pathways, we efficiently generated MGE cells vs. CGE cells from human PSCs, which predominantly generate Parvalbumin-expressing or Somatostatin-expressing interneurons vs. Calretinin-expressing interneurons, respectively. Efficient generation of specific differentiated progenies of hPSCs as shown in this study will be a pivotal step to realize the full potential of hPSCs for regenerative medicine, developmental studies, disease modeling, bioassay, and drug screening.

摘要

人类多能干细胞（PSCs）为在体外研究人类发育、在培养皿中模拟疾病、筛选药物以及提供无限且不受伦理阻碍的治疗细胞来源提供了契机。皮质GABA能中间神经元在胚胎发育过程中由内侧神经节隆起（MGE）细胞和尾侧神经节隆起（CGE）细胞产生，通过提供抑制性输入来调节皮质神经网络。它们的功能失调会导致无法精确调节神经回路平衡，这与精神分裂症、自闭症和癫痫等脑部疾病有关。在本研究中，我们通过对发育相关的背腹侧和头尾侧信号通路进行组合和时间调控，从人类PSCs中高效生成了MGE细胞和CGE细胞，它们分别主要产生表达小白蛋白的中间神经元或表达生长抑素的中间神经元，而不是表达钙视网膜蛋白的中间神经元。如本研究所示，高效生成hPSCs的特定分化后代将是实现hPSCs在再生医学、发育研究、疾病建模、生物测定和药物筛选方面全部潜力的关键一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/7084063b3fcd/nihms729636f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/79aba91296fe/nihms729636f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/493cfec085f0/nihms729636f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/077f19225be1/nihms729636f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/7084063b3fcd/nihms729636f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/41381e504f4f/nihms729636f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/84d8dfef5e2f/nihms729636f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/f0956529a8c1/nihms729636f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/79aba91296fe/nihms729636f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/493cfec085f0/nihms729636f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/077f19225be1/nihms729636f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1fb/4786472/7084063b3fcd/nihms729636f7.jpg

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