SC1 (Pluripotin) was identified in a cell-based chemical library screen for small molecules that regulate mouse embryonic stem (ES) cell self-renewal. SC1 is sufficient to sustain long-term self-renewal of mouse ES cells in an undifferentiated state in the absence of LIF, feeder cells, or serum. SC1 acts through dual inhibition of extracellular signal-regulated kinase 1 (ERK1) and Ras GTPase-activating protein (Ras-GAP). Mouse ES cells maintained in the presence of SC1 retain their ability to differentiate into cells representing all three germ layers in vitro, form chimeric mouse, and contribute to germ line in vivo.
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