Leukemia inhibitory factor

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Leukemia inhibitory factor
LIF Crystal Structure.rsh.png
PDB rendering based on 1LKI.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols LIF ; CDF; DIA; HILDA; MLPLI
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 P09056
RefSeq (mRNA) NM_001257135 NM_001039537
RefSeq (protein) NP_001244064 NP_001034626
Location (UCSC) Chr 22:
30.64 – 30.64 Mb
Chr 11:
4.26 – 4.27 Mb
PubMed search [1] [2]

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

Function[edit]

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 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[edit]

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.[3]

Expression[edit]

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. Recombinant LIF has been produced in plants by InVitria.

Use in stem cell culture[edit]

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 typically added to stem cell culture medium to reduce spontaneous differentiation.[4][5]

References[edit]

  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. 
  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. ^ Suman P, Malhotra SS, Gupta SK LIF-STAT signaling and trophoblast biology. JAKSTAT. 2013 Oct 1;2(4):e25155. Epub 2013 Jun 27.PMID:24416645.
  4. ^ Kawahara Y, Manabe T, Matsumoto M, Kajiume T, Matsumoto M, Yuge L (2009). "LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity". In Zwaka, Thomas. PLoS ONE 4 (7): e6343. doi:10.1371/journal.pone.0006343. PMC 2710515. PMID 19626124. 
  5. ^ "CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'". 

Application of recombinant human leukemia inhibitory factor (LIF)for maintenance of mouse embryonic stem cells; Journal of Biotechnology http://dx.doi.org/10.1016/j.jbiotec.2013.12.012

Further reading[edit]

External links[edit]