High Content Screening for Compounds that Induce Early Stages of Human Embryonic Stem Cell Differentiation
| Autor: | Thierry Dorval, Heekyoung Jeon, Jonathan Cechetto, JooHyun Jee, Peter Sommer, Zewon Park, Dong-Youn Hwang |
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| Přispěvatelé: | Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
MESH: Embryonic Stem Cells/cytology
MESH: Small Molecule Libraries/pharmacology Cellular differentiation Population Drug Evaluation Preclinical Context (language use) Biology Bioinformatics Stem cell marker 01 natural sciences Cell Line Small Molecule Libraries 03 medical and health sciences MESH: Software 0302 clinical medicine Drug Discovery Image Processing Computer-Assisted Humans education MESH: High-Throughput Screening Assays/methods Embryonic Stem Cells education.field_of_study MESH: Humans Organic Chemistry MESH: Embryonic Stem Cells/drug effects Cell Differentiation General Medicine Embryonic stem cell 0104 chemical sciences 3. Good health Computer Science Applications Cell biology High-Throughput Screening Assays MESH: Cell Line 010404 medicinal & biomolecular chemistry MESH: Drug Evaluation Preclinical/methods 030220 oncology & carcinogenesis High-content screening [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology MESH: Cell Differentiation/drug effects Stem cell MESH: Image Processing Computer-Assisted/methods Software |
| Zdroj: | Combinatorial Chemistry and High Throughput Screening Combinatorial Chemistry and High Throughput Screening, Bentham Science Publishers, 2012, 15 (8), pp.656-665. ⟨10.2174/138620712802650540⟩ |
| ISSN: | 1386-2073 |
| DOI: | 10.2174/138620712802650540⟩ |
| Popis: | Embryonic stem cells, due to their self-renewal and pluripotency properties, can be used to repair damaged tissues and as an unlimited source of differentiated cells. Although stem cells represent an important opportunity for cell based therapy and small molecules screening (in the context of drug or target discovery) many drawbacks are still preventing their widespread use. One of the most significant limitations is related to the complexity, as well as the reliability, of current protocols driving stem cells into any homogeneously differentiated cellular population. In this respect there is a strong demand for molecular agents promoting differentiation and thereby enabling robust, efficient and safe production of differentiated cells. In order to identify novel molecules that enhance early stages of differentiation, we developed an image based high content screening (HCS) approach using human embryonic stem cells (hESC). In our approach, we took advantage of custom image mining software specifically adapted for the selection of stem cell differentiation agents and the rejection of false positive hits. As a proof of concept -3500 small molecules originating from commercial libraries were screened and a number of molecules of interests were identified. These molecules show stem cell differentiation properties comparable to the phenotypic signature obtained with the reference compound retinoic acid. |
| Databáze: | OpenAIRE |
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