Leukemia inhibitory factor

Overview
Leukemia inhibitory factor, or LIF, an interleukin 6 class cytokine, is a chemical in cells that affects their growth and development.

Function
LIF derives its name from its ability to induce the terminal differentiation of myeloid leukaemic cells. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone metabolism, cachexia, neural development, embryogenesis and inflammation.

Binding/activation
LIF binds to the specific LIF receptor (LIFR-&alpha;) which forms a heterodimer with a specific subunit common to all members of that family of receptors, the GP130 signal transducing subunit. This leads to activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen activated protein kinase) cascades.

Expression
LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell mass. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF.

Use in stem cell culture
Removal of LIF pushes stem cells toward differentiation, but they retain their proliferative potential. Therefore LIF is used in mouse embryonic stem cell culture. It is necessary to maintain the stem cells in an undifferentiated state, however genetic manipulation of embryonic stem cells allows for Lif independent growth, notably overexpression of the gene Nanog.

Lif is not required for culture of human embryonic stem cells.