High-Content Phenotypic Screening and Triaging Strategy to Identify Small Molecules Driving Oligodendrocyte Progenitor Cell Differentiation

We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell–like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 nontoxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation.

Source: Journal of Biomolecular Screening - February 19, 2015 Category: Molecular Biology Authors: Peppard, J. V., Rugg, C. A., Smicker, M. A., Powers, E., Harnish, E., Prisco, J., Cirovic, D., Wright, P. S., August, P. R., Chandross, K. J. Tags: Original Research Source Type: research