Anti-leukemia factor

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PDB 3D LIF structure

Anti-Leukemia Factor , or LIF , is an interleukin-6 class cytokine that inhibits cell growth through differentiation. When the amount of LIF falls, the cells differentiate.

function

The name LIF comes from the ability of the molecule to initiate the terminal differentiation of myeloid leukemia cells and thus prevent uninhibited growth. Other properties of the cytokine are: growth promotion and cell differentiation of different cells, influence on bones, nerve cell development, embryogenesis and inflammatory processes. LIF, which is regulated by p53 , also appears to facilitate embryo implantation.

Attachment / activation

LIF binds to its receptor LIFR-α, which forms a heterodimer with the GP130 subunit. This leads to the activation of the JAK / STAT ( Janus kinase / signal transducer and activator of transcription ) and MAPK ( mitogen activated protein kinase ) cascade.

Expression

LIF is normally produced in the trophectoderm of the developing embryo, with the LIF receptor being found in the internal cell mass (ICM, embryoblast ). Since embryonic stem cells come out of the inner cell mass during the blastocyst phase, removal of the stem cells also leads to the loss of the LIF source.

Use in stem cell culture

Removal of the LIF leads to differentiation of the cells, but they retain their growth potential and pluripotency. That is why it is added to embryonic stem cell culture (from mice). It is important here to keep the cells in an undifferentiated state. If the Nanog gene is overexpressed, stem cells can also be kept without LIF. LIF is usually added to the cell culture medium in order to prevent the embryonic stem cells from differentiating.

See also

Individual evidence

  1. ^ Douglas J. Hilton: LIF: lots of interesting functions . In: Trends in Biochemical Sciences . tape 17 , no. 2 , February 1992, p. 72-76 , doi : 10.1016 / 0968-0004 (92) 90505-4 .
  2. ↑ Ralf Linker, Ralf Gold, Fred Luhder: Function of Neurotrophic Factors Beyond the Nervous System: Inflammation and Autoimmune Demyelination . In: Critical Reviews in Immunology . tape 29 , no. 1 , 2009, p. 43-68 , doi : 10.1615 / CritRevImmunol.v29.i1.20 , PMID 19348610 .
  3. ↑ Wenwei Hu, Zhaohui Feng, Angelika K. Teresky1, Arnold J. Levine: p53 regulates maternal reproduction through LIF . In: Nature . 450, No. 7170, 2007, pp. 721-724. doi : 10.1038 / nature05993 . PMID 18046411 .
  4. ↑ Cristina Nogueira Silva, Paulina C. Piairo, Emanuel Carvalho Dias, Carla Veiga, Rute S. Moura, Jorge Correia Pinto: The role of glycoprotein 130 family of cytokines in fetal rat lung development . June 2013, doi : 10.1371 / journal.pone.0067607 .
  5. ↑ Pankaj Suman, Sudha Saryu Malhotra, Satish Kumar Gupta: LIF-STAT signaling and trophoblast biology . In: JAK-STAT . tape 2 , no. 4 , June 27, 2013, p. e25155 , doi : 10.4161 / jkst.25155 , PMID 24416645 .
  6. ↑ Lusine Aghajanova: Leukemia Inhibitory Factor and Human Embryo Implantation . In: Annals of the New York Academy of Sciences . tape 1034 , no. 1 , December 1, 2004, p. 176-183 , doi : 10.1196 / annals.1335.020 .
  7. ↑ Yumi Kawahara, Tomotaka Manabe, Masaya Matsumoto, Teruyuki Kajiume, Masayasu Matsumoto, Louis Yuge: LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity . In: PLoS ONE . tape 4 , no. 7 , July 23, 2009, p. e6343 , doi : 10.1371 / journal.pone.0006343 , PMID 19626124 , PMC 2710515 (free full text).
  8. ↑ CGS: PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts' . Retrieved May 1, 2014.
  9. ^ Christoffer Tamm, Sara Pijuan Galitó, Cecilia Annerén: A Comparative Study of Protocols for Mouse Embryonic Stem Cell Culturing . In: PLoS ONE . tape 8 , no. 12 , December 10, 2013, p. e81156 , doi : 10.1371 / journal.pone.0081156 .