Dorsomorphin Promotes Human Embryonic Stem Cell Self-Renewal

摘要

Human embryonic stem cells (hESCs), derived from the inner cell mass (ICM) of the blastocyst, have the capacity for long-term undifferentiated growth in culture and the theoretical potential to differentiate into all somatic cell types. These hESCs offer not only a model system for human development, but also a potentially unlimited source of graft material for transplantation-based therapies. Long-term hESCs can be supported using feeder-fibroblast conditioned medium (CM), or high concentrations of basic FGF, PEDF, or TGF-β/activin/Nodal proteins. Recently, small molecules that can support mouse embryonic stem cell self-renewal and hESC self-renewal have been reported. Unfortunately, none of the reported small molecules is able to support long-term hESC self-renewal (five or more passages) under defined culture conditions without bFGF or TGF-β/activin/Nodal proteins. Consequently, unbiased cellular screens for small molecules that regulate long-term hESC self-renewal may provide new insights into stem cell biology, and also facilitate practical applications of ES cells in research and therapy. Herein, we report the identification of a small molecule that promotes long-term hESC self-renewal.