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用于细胞和分子特征分析的人类诱导多能干细胞源性脑类器官的生成。

Generation of human induced pluripotent stem cell-derived cerebral organoids for cellular and molecular characterization.

机构信息

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.

出版信息

STAR Protoc. 2022 Feb 8;3(1):101173. doi: 10.1016/j.xpro.2022.101173. eCollection 2022 Mar 18.

DOI:10.1016/j.xpro.2022.101173
PMID:35199037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8844852/
Abstract

Human induced pluripotent stem cell (hiPSC)-derived cerebral organoids (COs) can serve as an model for studying normal and pathologic human brain development. Here, we optimized existing protocols to streamline the generation of forebrain COs from hiPSCs. We employ these COs to define the impact of disease-causing mutations on cell fate, differentiation, maturation, and morphology relevant to neurodevelopmental disorders. Although limited to forebrain CO identity, this schema requires minimal external interference and is amenable to low-throughput biochemical assays. For complete details on the use and execution of this profile, please refer to Anastasaki et al. (2020) and Wegscheid et al. (2021).

摘要

人诱导多能干细胞(hiPSC)衍生的大脑类器官(COs)可以作为研究正常和病理人类大脑发育的模型。在这里,我们优化了现有的方案,以简化从 hiPSC 生成前脑 CO 的过程。我们使用这些 CO 来定义致病突变对与神经发育障碍相关的细胞命运、分化、成熟和形态的影响。尽管仅限于前脑 CO 的特性,但该方案需要最小的外部干扰,并且适用于低通量生化分析。有关此方案的使用和执行的完整详细信息,请参考 Anastasaki 等人(2020 年)和 Wegscheid 等人(2021 年)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/7114e0a11a54/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/55ffee33b9a9/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/2f52d3b38a73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/44c14ad78d0d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/a49635ced07d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/a107609e5bf8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/7114e0a11a54/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/55ffee33b9a9/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/2f52d3b38a73/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/44c14ad78d0d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/a49635ced07d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/a107609e5bf8/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a16e/8844852/7114e0a11a54/gr5.jpg

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Patient-derived iPSC-cerebral organoid modeling of the 17q11.2 microdeletion syndrome establishes CRLF3 as a critical regulator of neurogenesis.患者来源的 iPSC-脑类器官模型模拟 17q11.2 微缺失综合征,确定了 CRLF3 作为神经发生的关键调节因子。
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