identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hescs but not dopamine neurons识别的自动筛选小分子选择性地消除神经干细胞来源于为但不是多巴胺神经元.pdfVIP

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identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hescs but not dopamine neurons识别的自动筛选小分子选择性地消除神经干细胞来源于为但不是多巴胺神经元.pdf

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identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hescs but not dopamine neurons识别的自动筛选小分子选择性地消除神经干细胞来源于为但不是多巴胺神经元

Identification by Automated Screening of a Small Molecule that Selectively Eliminates Neural Stem Cells Derived from hESCs but Not Dopamine Neurons 1 1 1 2 1 3 1,2 Yi Han , Aaron Miller , Julie Mangada , Ying Liu , Andrzej Swistowski , Ming Zhan , Mahendra S. Rao , Xianmin Zeng1* 1 Buck Institute for Aging Research, Novato, California, United States of America, 2 Invitrogen, Carlsbad, California, United States of America, 3 National Institute of Aging, Baltimore, Maryland, United States of America Abstract Background: We have previously described fundamental differences in the biology of stem cells as compared to other dividing cell populations. We reasoned therefore that a differential screen using US Food and Drug Administration (FDA)- approved compounds may identify either selective survival factors or specific toxins and may be useful for the therapeutically-driven manufacturing of cells in vitro and possibly in vivo. Methodology/Principal Findings: In this study we report on optimized methods for feeder-free culture of hESCs and hESC- derived neural stem cells (NSCs) to facilitate automated screening. We show that we are able to measure ATP as an indicator of metabolic activity in an automated screening assay. With this optimized platform we screened a collection of FDA- approved drugs to identify compounds that have differential toxicity to hESCs and their neural derivatives. Nine compounds were identified to be specifically toxic for NSCs to a greater extent than for hESCs. Six of these initial hits were retested and verified by large-scale cell culture to determine dose-responsive NSC toxicity. One of the compounds retest