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
External IDs OMIM159540 MGI96787 HomoloGene1734 GeneCards: LIF Gene
RNA expression pattern
PBB GE LIF 205266 at tn.png
More reference expression data
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:
30.24 – 30.25 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.


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]


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]


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]


  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 (1): 176–83. doi:10.1196/annals.1335.020. PMID 15731310. 
  3. ^ Suman P, Malhotra SS, Gupta SK (Oct 2013). "LIF-STAT signaling and trophoblast biology". JAKSTAT. 2 (4): e25155. doi:10.4161/jkst.25155. PMID 24416645. 
  4. ^ 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. 
  5. ^ "CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'". 
  • Author A. "Application of recombinant human leukemia inhibitory factor (LIF)for maintenance of mouse embryonic stem cells". Journal of Biotechnology 172: 67–72. doi:10.1016/j.jbiotec.2013.12.012. 

Further reading[edit]

  • Patterson PH (1994). "Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology". Proc. Natl. Acad. Sci. U.S.A. 91 (17): 7833–5. doi:10.1073/pnas.91.17.7833. PMC 44497. PMID 8058719. 
  • Aghajanova L (2005). "Leukemia inhibitory factor and human embryo implantation". Ann. N. Y. Acad. Sci. 1034 (1): 176–83. doi:10.1196/annals.1335.020. PMID 15731310. 
  • Králícková M, Síma P, Rokyta Z (2005). "Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium". Folia Microbiol. (Praha) 50 (3): 179–86. doi:10.1007/BF02931563. PMID 16295654. 
  • Stahl J, Gearing DP, Willson TA et al. (1990). "Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions". J. Biol. Chem. 265 (15): 8833–41. PMID 1692837. 
  • Bazan JF (1991). "Neuropoietic cytokines in the hematopoietic fold". Neuron 7 (2): 197–208. doi:10.1016/0896-6273(91)90258-2. PMID 1714745. 
  • Lowe DG, Nunes W, Bombara M et al. (1989). "Genomic cloning and heterologous expression of human differentiation-stimulating factor". DNA 8 (5): 351–9. doi:10.1089/dna.1.1989.8.351. PMID 2475312. 
  • Sutherland GR, Baker E, Hyland VJ et al. (1989). "The gene for human leukemia inhibitory factor (LIF) maps to 22q12". Leukemia 3 (1): 9–13. PMID 2491897. 
  • Mori M, Yamaguchi K, Abe K (1989). "Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia". Biochem. Biophys. Res. Commun. 160 (3): 1085–92. doi:10.1016/S0006-291X(89)80114-7. PMID 2730639. 
  • Gough NM, Gearing DP, King JA et al. (1988). "Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2623–7. doi:10.1073/pnas.85.8.2623. PMC 280050. PMID 3128791. 
  • Williams RL, Hilton DJ, Pease S et al. (1989). "Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells". Nature 336 (6200): 684–7. doi:10.1038/336684a0. PMID 3143916. 
  • Moreau JF, Donaldson DD, Bennett F et al. (1989). "Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells". Nature 336 (6200): 690–2. doi:10.1038/336690a0. PMID 3143918. 
  • Yamaguchi M, Miki N, Ono M et al. (1995). "Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer". Endocrinology 136 (3): 1072–8. doi:10.1210/en.136.3.1072. PMID 7867561. 
  • Schmelzer CH, Harris RJ, Butler D et al. (1993). "Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor". Arch. Biochem. Biophys. 302 (2): 484–9. doi:10.1006/abbi.1993.1243. PMID 8489250. 
  • Aikawa J, Ikeda-Naiki S, Ohgane J et al. (1997). "Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy". Biochim. Biophys. Acta 1353 (3): 266–76. doi:10.1016/s0167-4781(97)00079-1. PMID 9349722. 
  • Hinds MG, Maurer T, Zhang JG et al. (1998). "Solution structure of leukemia inhibitory factor". J. Biol. Chem. 273 (22): 13738–45. doi:10.1074/jbc.273.22.13738. PMID 9593715. 
  • "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074. 
  • Tanaka M, Hara T, Copeland NG et al. (1999). "Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit". Blood 93 (3): 804–15. PMID 9920829. 
  • Nakashima K, Yanagisawa M, Arakawa H et al. (1999). "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300". Science 284 (5413): 479–82. doi:10.1126/science.284.5413.479. PMID 10205054. 
  • Dunham I, Shimizu N, Roe BA et al. (1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208. 

External links[edit]