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Abstract
Grant Number: 1R21NS053655-01 Project Title: HTS Screen-Neural Differentiation in Human ES Cells(RMI)
PI Information: Name Title STUDER, LORENZ P. studerl@mskcc.org ASSISTANT PROFESSOR Abstract: DESCRIPTION (provided by applicant): The goal of this study is to develop a high throughput (HTS) assay to identify chemical compounds that induce or repress neural differentiation of human embryonic stem (hES) cells. The proposal is based on i) the need to identify agents that drive lineage specific differentiation in hES cells, ii) our ability to generate lineage specific reporter ES lines using BAC transgenesis, iii) improved protocols for the standardized growth of hEScells, iv) the availability of state-of-the-art robotic and screening tools for HTS implementation. This study should be a proof-of-principle application for the use of HTS assays to study early human development, provide novel insights into the pathways that control neural differentiation, and offer a prototype application for hES cell based HTS assays the will include future assays based on the use of our in-house generated siRNA library. The Specific Aims of the study are: 1. Generation of BAG transgenic human ES cell reporter lines for HTS assay (line WA-09) 2. Assay development to HTS format (line WA-09) 3. Biological validations and secondary screens of candidate compounds, (lines WA-09, WA-01, ES-03, ES-04. SA-01, SA-02, MI-01). The identification of novel compounds that direct neural differentiation of hES cells under defined in vitro conditions will also be an important contribution to translational stem cell efforts. Of particular importance will be the development of neural differentiation conditions that obviate the use of embryoid body formation or stromal mouse feeder co-culture protocols. Defined compound based neural differentiation may ultimately provide the most reproducible and safe differentiation strategy for future clinical applications.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
cell differentiation, drug screening /evaluation, high throughput technology, human embryonic stem cell line, neuron, technology /technique development
artificial chromosome, biotechnology, green fluorescent protein, immunocytochemistry
Institution: SLOAN-KETTERING INSTITUTE FOR CANCER RES 1275 YORK AVE NEW YORK, NY 10065 Fiscal Year: 2005 Department: Project Start: 30-SEP-2005 Project End: 31-AUG-2007 ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE IRG: ZNS1