Mouse ES cells and human ES cells were both originally derived and grown on a layer of mouse fibroblasts (called ?feeder cells?) in the presence of bovine serum. However the factors that sustain the growth of these two cell types appear to be distinct. The addition of the cytokine leukemia inhibitory factor (LIF) to serumcontaining medium allows mouse ES cells to proliferate in the absence of feeder cells. LIF modulates mouse ES cells through the activation of STAT3 (signal transducers and activators of transcription) protein. In serum-free culture however LIF alone is insufficient to prevent mouse ES cells from differentiating into neural cells. Recently Ying et al. reported that the combination of bone morphogenetic proteins (BMPs) and LIF is sufficient to support the self-renewal of mouse ES cells.12 The effects of BMPs on mouse ES cells involve induction of inhibitor of differentiation (Id) proteins and inhibition of extracellular receptor kinase (ERK) and p38 mitogen-activated protein kinases (MAPK).1213 However LIF in the presence of serum is not sufficient to promote the self-renewal of human ES cells3 and the LIF/STAT3 pathway appears to be inactive in undifferentiated human ES cells.1415 Also the addition of BMPs to human ES cells in conditions that would otherwise support ES cells leads to the rapid differentiation of human ES cells.1617
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