Novel Scalable and Simplified System to Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells.
Novel Scalable and Simplified System to Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells.
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DOI：
10.3389/fncel.2021.682272
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发表时间：
2021
影响因子：
5.3
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Bodnar B;Zhang Y;Liu J;Lin Y;Wang P;Wei Z;Saribas S;Zhu Y;Li F;Wang X;Yang W;Li Q;Ho WZ;Hu W
人脑类器官（CO）是一个三维（3D）细胞培养系统，重现了发育中的人脑。虽然CO已被证明是一种非常宝贵的工具，用于研究神经系统疾病在临床上更相关的问题，仍然有几个缺点，包括CO的变异性和可重复性，以及缺乏或代表性不足的某些细胞类型通常发现在大脑中。随着生成CO的技术不断改进，更高效和简化的协议已经解决了其中的一些问题。在这里，我们提出了一种新的可扩展和简化的系统，以产生含小胶质细胞的CO（MCO）。我们表征了MCO的细胞类型和动态发育，并验证了这些MCO含有小胶质细胞、星形胶质细胞、神经元和神经干/祖细胞，以反映人脑发育的方式成熟。我们介绍了一种直接从诱导多能干细胞（iPSC）产生胚状体（EB）的新技术，该技术涉及直接从3D培养物以及标准6孔培养板中的轨道振荡培养物过渡的简化步骤。这使得MCO的生成具有易于使用的系统，该系统是负担得起的，并且任何普通实验室都可以访问。
Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell types and dynamic development of MCOs and validate that these MCOs harbor microglia, astrocytes, neurons, and neural stem/progenitor cells, maturing in a manner that reflects human brain development. We introduce a novel technique for the generation of embryoid bodies (EBs) directly from induced pluripotent stem cells (iPSCs) that involves simplified steps of transitioning directly from 3D cultures as well as orbital shaking culture in a standard 6-well culture plate. This allows for the generation of MCOs with an easy-to-use system that is affordable and accessible by any general lab.
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影响因子：
11
作者：
de Vrij FM;Bouwkamp CG;Gunhanlar N;Shpak G;Lendemeijer B;Baghdadi M;Gopalakrishna S;Ghazvini M;Li TM;Quadri M;Olgiati S;Breedveld GJ;Coesmans M;Mientjes E;de Wit T;Verheijen FW;Beverloo HB;Cohen D;Kok RM;Bakker PR;Nijburg A;Spijker AT;Haffmans PMJ;Hoencamp E;Bergink V;GROUP Study Consortium;Vorstman JA;Wu T;Olde Loohuis LM;Amin N;Langen CD;Hofman A;Hoogendijk WJ;van Duijn CM;Ikram MA;Vernooij MW;Tiemeier H;Uitterlinden AG;Elgersma Y;Distel B;Gribnau J;White T;Bonifati V;Kushner SA
通讯作者：
Kushner SA
影响因子：
23.9
作者：
Bershteyn M;Nowakowski TJ;Pollen AA;Di Lullo E;Nene A;Wynshaw-Boris A;Kriegstein AR
通讯作者：
Kriegstein AR
影响因子：
8.8
作者：
Garcia-Reitboeck P;Phillips A;Piers TM;Villegas-Llerena C;Butler M;Mallach A;Rodrigues C;Arber CE;Heslegrave A;Zetterberg H;Neumann H;Neame S;Houlden H;Hardy J;Pocock JM
通讯作者：
Pocock JM
影响因子：
5.9
作者：
Douvaras P;Sun B;Wang M;Kruglikov I;Lallos G;Zimmer M;Terrenoire C;Zhang B;Gandy S;Schadt E;Freytes DO;Noggle S;Fossati V
通讯作者：
Fossati V
影响因子：
4.6
作者：
Gouder, Laura;Vitrac, Aline;Cloez-Tayarani, Isabelle
通讯作者：
Cloez-Tayarani, Isabelle