Human Epilepsy Tools Core (HETC)

人类癫痫工具核心 (HETC)

基本信息

批准号：
10455561
负责人：
MICHAEL D UHLER
金额：
$ 37.92万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10455561
关键词：
3-Dimensional Astrocytes Blood CRISPR/Cas technology Cell Differentiation process Cell Line Cells Clone Cells Clustered Regularly Interspaced Short Palindromic Repeats Core Facility Deletion Mutation Derivation procedure Development Disease model Doxycycline Embryo Engineering Epilepsy Fibroblasts Floor Funding Gene Mutation Generations Genes Genetic Genomics Glutamates Human Human Resources Individual Knock-in Knock-out Laboratories Lead Mediating Methods Michigan Modeling Motor Neurons Mutagenesis Mutation Neurologic Neurology Neuronal Differentiation Neurons Organoids Parents Pathogenicity Patients Peripheral Peripheral Blood Mononuclear Cell Play Procedures Protocols documentation Quality Control Research Research Personnel Resources Role Sampling Scientist Services Southern Blotting Specific qualifier value Standardization Techniques Testing Tissues Training Transgenes Transgenic Organisms Universities Validation Variant Work cell type design developmental disease differentiation protocol directed differentiation experience expression vector gene interaction genetic variant genome editing human embryonic stem cell human embryonic stem cell line human pluripotent stem cell human stem cells in vitro testing induced pluripotent stem cell insertion/deletion mutation medical schools mutant nerve stem cell nervous system disorder novel novel strategies operation pluripotency regenerative therapy relating to nervous system repository skills stem cell model stem cells tool transgene expression vector

项目摘要

HUMAN EPILEPSY TOOLS CORE (HETC) Both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hIPSCs) represent important models for human disorders of the nervous system. Dr. Michael Uhler will serve as the Director and Dr. Jack Parent will serve as the Co-Director of the HETC which is housed within the UM Neurology Department. The HETC will provide support to the three projects of the EpiMVP by providing stem cell models and differentiation methods for the characterization of epilepsy genes and their variants of unknown significant (VUS). Specifically, the HETC will provide validated heterozygous and homozygous hESC mutant lines for these genes as well as doxycycline-inducible transgenic lines that express the wildtype and VUS for each gene. In addition, the HETC will derive patient iPSC lines for the genes from either fibroblasts or blood. Finally, the HETC will standardize and optimize both 2D and 3D neuronal differentiation protocols for use by the investigators in Projects 1 and 2. Thus, the HETC will serve as a central repository and resource for human stem cell derivation while providing significant economy as well as quality control for stem cell work within the two projects.

人类癫痫工具核心 (HETC) 人类胚胎干细胞 (hESC) 和人类诱导多能干细胞（hIPSC）代表了人类神经系统疾病的重要模型。迈克尔博士 Uhler 将担任 HETC 主任，Jack Parent 博士将担任 HETC 联合主任它位于密歇根大学神经内科。 HETC将提供支持 EpiMVP 的三个项目通过提供干细胞模型和分化方法为癫痫基因及其未知显着性变异（VUS）的表征。具体来说， HETC 将为这些提供经过验证的杂合和纯合 hESC 突变系基因以及表达野生型和 VUS 的多西环素诱导转基因系每个基因。此外，HETC 还将从患者 iPSC 系中获得基因成纤维细胞或血液。最后，HETC 将标准化和优化 2D 和 3D 神经元供项目 1 和 2 的研究人员使用的分化方案。因此，HETC 将作为人类干细胞衍生的中央存储库和资源，同时提供这两个项目中的干细胞工作具有显着的经济性和质量控制。