High Content Screening for Compounds that Induce Early Stages of Human Embryonic Stem Cell Differentiation.
Résumé
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 uses. 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 prove of concept we screened ~3500 small molecules originating from commercial libraries and were able to identify molecules of interests that show stem cell differentiation properties comparable to the phenotypic signature obtained with retinoic acid.