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Leukemia inhibitory factor

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Title: Leukemia inhibitory factor  
Author: World Heritage Encyclopedia
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Subject: STAT3, Stem cell, Outline of immunology, LIF, SOX2
Collection: Cytokines, Oncology, Pharmacology
Publisher: World Heritage Encyclopedia

Leukemia inhibitory factor

Leukemia inhibitory factor
PDB rendering based on 1LKI.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs GeneCards:
RNA expression pattern
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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 1
  • Binding/activation 2
  • Expression 3
  • Use in stem cell culture 4
  • References 5
  • Further reading 6
  • External links 7


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.

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 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.  
  2. ^ Aghajanova, L (2004). "Leukemia inhibitory factor and human embryo implantation". Annals of the New York Academy of Sciences 1034 (1): 176–83.  
  3. ^ Suman P, Malhotra SS, Gupta SK (Oct 2013). "LIF-STAT signaling and trophoblast biology". JAKSTAT. 2 (4): e25155.  
  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.  
  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.  

Further reading

  • 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.  
  • Aghajanova L (2005). "Leukemia inhibitory factor and human embryo implantation". Ann. N. Y. Acad. Sci. 1034 (1): 176–83.  
  • 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.  
  • 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.  
  • Bazan JF (1991). "Neuropoietic cytokines in the hematopoietic fold". Neuron 7 (2): 197–208.  
  • Lowe DG, Nunes W, Bombara M, et al. (1989). "Genomic cloning and heterologous expression of human differentiation-stimulating factor". DNA 8 (5): 351–9.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Hinds MG, Maurer T, Zhang JG, et al. (1998). "Solution structure of leukemia inhibitory factor". J. Biol. Chem. 273 (22): 13738–45.  
  • "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1999.  
  • 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.  
  • 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.  
  • Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95.  

External links

  • Leukemia Inhibitory Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Source of Recombiant Leukemia Inhibitory Factor ( )
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