High Content Screening for Compounds that Induce Early Stages of Human Embryonic Stem Cell Differentiation
2012
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.
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