Leukemia inhibitory factor

Leukemia inhibitory factor
Leukemia inhibitory factor (cholinergic differentiation factor)

PDB rendering based on 1LKI.
Identifiers
Symbols LIF; CDF; DIA; HILDA
External IDs OMIM159540 MGI96787 HomoloGene1734 GeneCards: LIF Gene
RNA expression pattern
PBB GE LIF 205266 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3976 16878
Ensembl ENSG00000128342 ENSMUSG00000034394
UniProt P15018 Q3U1H5
RefSeq (mRNA) NM_002309.3 NM_001039537
RefSeq (protein) NP_002300.1 NP_001034626
Location (UCSC) Chr 22:
30.64 – 30.64 Mb
Chr 11:
4.16 – 4.17 Mb
PubMed search [1] [2]

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

Contents

Function

LIF derives its name from its ability to induce the terminal differentiation of myeloid leukemic 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. p53 regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans.[1] It has been suggested that recombinant human LIF might help to improve the implantation rate in women with unexplained infertility.[2]

Binding/activation

LIF binds to the specific LIF receptor (LIFR-α) 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 or pluripotency. 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.[3][4]

References

  1. ^ Wenwei Hu, Zhaohui Feng, Angelika K. Teresky1, Arnold J. Levine (November 29, 2007). "p53 regulates maternal reproduction through LIF". Nature 450 (7170): 721–724. doi:10.1038/nature05993. PMID 18046411. http://www.nature.com/nature/journal/v450/n7170/abs/nature05993.html. 
  2. ^ Aghajanova, L (2004). "Leukemia inhibitory factor and human embryo implantation". Annals of the New York Academy of Sciences 1034: 176–83. doi:10.1196/annals.1335.020. PMID 15731310. 
  3. ^ Kawahara Y, Manabe T, Matsumoto M, Kajiume T, Matsumoto M, Yuge L (2009). Zwaka, Thomas. ed. "LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity". PLoS ONE 4 (7): e6343. doi:10.1371/journal.pone.0006343. PMC 2710515. PMID 19626124. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006343. 
  4. ^ "CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'". http://www.geneticsandsociety.org/article.php?id=5197. 

Further reading

External links


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