Leukemia inhibitory factor

Leukemia inhibitory factor, or LIF, is an is_associated_with::interleukin 6 class is_associated_with::cytokine that affects cell growth by inhibiting differentiation. When LIF levels drop, the cells differentiate.

Function
LIF derives its name from its ability to induce the terminal differentiation of myeloid leukemic cells, thus preventing their continued growth. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on is_associated_with::bone is_associated_with::metabolism, is_associated_with::cachexia, is_associated_with::neural development, is_associated_with::embryogenesis and is_associated_with::inflammation. is_associated_with::p53 regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans. It has been suggested that recombinant human LIF might help to improve the implantation rate in women with unexplained infertility.

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

Expression
LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the is_associated_with::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. Recombinant LIF has been produced in plants by InVitria.

Use in stem cell culture
Removal of LIF pushes stem cells toward differentiation, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic is_associated_with::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 is_associated_with::Nanog.

LIF is typically added to stem cell culture medium to reduce spontaneous differentiation.