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白血病抑制因子

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Leukemia inhibitory factor
白血病抑制因子
PDB rendering based on 1LKI.
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 LIF; CDF; DIA; HILDA; MLPLI
扩展标识 遗传学159540 鼠基因96787 同源基因1734 GeneCards: LIF Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 3976 16878
Ensembl ENSG00000128342 ENSMUSG00000034394
UniProt P15018 P09056
mRNA序列 NM_001257135 NM_001039537
蛋白序列 NP_001244064 NP_001034626
基因位置 Chr 22:
30.64 – 30.64 Mb
Chr 11:
4.26 – 4.27 Mb
PubMed查询 [1] [2]

白血病抑制因子(Leukemia inhibitory factor,缩写 LIF)是一种属于白介素-6英语interleukin 6大类的细胞因子。它能通过抑制分化影响细胞生长。LIF水平下降会使细胞开始分化。

功能

白血病抑制因子能够诱导骨髓性白血病细胞的末端分化,进而阻止其生长,因而得名。白血病抑制因子还有以下功能:能促进多种细胞的生长与分化,影响代谢、恶病质体、神经发育英语Neural development胚胎发育以及炎症作用。受p53调控的白血病抑制因子能促进小鼠和人的胚胎着床[1]。一篇文章提出重组人白血病抑制因子可能可以提高意外怀孕的妇女(体内胚胎)的着床成功率[2]

表达

LIF在正常情况下会由囊胚中的滋养层(TE)表达,而其受体LIFR则会由内细胞群(ICM)的细胞表达。胚胎干细胞取自内细胞群的细胞,在体外培养时就需要额外补充LIF。目前,重组LIF已可以通过基因工程的手段由植物(水稻)产生[3]

干细胞培养

干细胞培养基中大都含有LIF,可用于替代喂养层(feeder layer)细胞,因为喂养层细胞的主要作用即产生LIF。不表达LIF基因的喂养层细胞难以支持干细胞的培养[4]。LIF通过招募信号诱导分子以及转录激活因子3(STAT3)促进细胞的自我更新。活化的LIFR能征募Stat3。随后,JAK激酶能将其磷酸化。不过LIF和Stat3是不足以阻止细胞分化的,一旦移去培养基中的血清,干细胞就会分化。在原生多能性干细胞分化的可逆阶段,加入LIF可以使细胞重回原生多能性阶段[5][6][7]

参考

  1. ^ Wenwei Hu, Zhaohui Feng, Angelika K. Teresky1, Arnold J. Levine. p53 regulates maternal reproduction through LIF. Nature. November 29, 2007, 450 (7170): 721–724. PMID 18046411. doi:10.1038/nature05993. 
  2. ^ Aghajanova, L. Leukemia inhibitory factor and human embryo implantation. Annals of the New York Academy of Sciences. 2004, 1034: 176–83. PMID 15731310. doi:10.1196/annals.1335.020. 
  3. ^ Bradford A. Youngblood; 等. Application of recombinant human leukemia inhibitory factor (LIF) produced in rice (Oryza sativa L.) for maintenance of mouse embryonic stem cells. Journal of Biotechnology Volume 172. 2014-02-20: 67–72. 
  4. ^ Stewart, C. L.; Kaspar, P; Brunet, L. J.; Bhatt, H; Gadi, I; Köntgen, F; Abbondanzo, S. J. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature. 1992, 359 (6390): 76–9. PMID 1522892. doi:10.1038/359076a0. 
  5. ^ Martello, Graziano; Smith, Austin. The Nature of Embryonic Stem Cells. Annual Review Cell Developmental Biology. 2014, 30: 647. doi:10.1146/annurev-cellbio-100913-013116. 
  6. ^ Kawahara Y, Manabe T, Matsumoto M, Kajiume T, Matsumoto M, Yuge L. Zwaka, Thomas, 编. LIF-Free Embryonic Stem Cell Culture in Simulated Microgravity. PLoS ONE. 2009, 4 (7): e6343. PMC 2710515. PMID 19626124. doi:10.1371/journal.pone.0006343. 
  7. ^ CGS : PTO Finds Stem Cell Patent Anticipated, Obvious in Light of 'Significant Guideposts'. (原始内容存档于2011-10-04). 

拓展阅读

  • Patterson PH. Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology. Proc. Natl. Acad. Sci. U.S.A. 1994, 91 (17): 7833–5. PMC 44497. PMID 8058719. doi:10.1073/pnas.91.17.7833. 
  • Aghajanova L. Leukemia inhibitory factor and human embryo implantation. Ann. N. Y. Acad. Sci. 2005, 1034: 176–83. PMID 15731310. doi:10.1196/annals.1335.020. 
  • Králícková M, Síma P, Rokyta Z. 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). 2005, 50 (3): 179–86. PMID 16295654. doi:10.1007/BF02931563. 
  • Stahl J, Gearing DP, Willson TA; 等. Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions. J. Biol. Chem. 1990, 265 (15): 8833–41. PMID 1692837. 
  • Bazan JF. Neuropoietic cytokines in the hematopoietic fold. Neuron. 1991, 7 (2): 197–208. PMID 1714745. doi:10.1016/0896-6273(91)90258-2. 
  • Lowe DG, Nunes W, Bombara M; 等. Genomic cloning and heterologous expression of human differentiation-stimulating factor. DNA. 1989, 8 (5): 351–9. PMID 2475312. doi:10.1089/dna.1.1989.8.351. 
  • Sutherland GR, Baker E, Hyland VJ; 等. The gene for human leukemia inhibitory factor (LIF) maps to 22q12. Leukemia. 1989, 3 (1): 9–13. PMID 2491897. 
  • Mori M, Yamaguchi K, Abe K. Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia. Biochem. Biophys. Res. Commun. 1989, 160 (3): 1085–92. PMID 2730639. doi:10.1016/S0006-291X(89)80114-7. 
  • Gough NM, Gearing DP, King JA; 等. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor. Proc. Natl. Acad. Sci. U.S.A. 1988, 85 (8): 2623–7. PMC 280050. PMID 3128791. doi:10.1073/pnas.85.8.2623. 
  • Williams RL, Hilton DJ, Pease S; 等. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature. 1989, 336 (6200): 684–7. PMID 3143916. doi:10.1038/336684a0. 
  • Moreau JF, Donaldson DD, Bennett F; 等. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature. 1989, 336 (6200): 690–2. PMID 3143918. doi:10.1038/336690a0. 
  • Yamaguchi M, Miki N, Ono M; 等. Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer. Endocrinology. 1995, 136 (3): 1072–8. PMID 7867561. doi:10.1210/en.136.3.1072. 
  • Schmelzer CH, Harris RJ, Butler D; 等. Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor. Arch. Biochem. Biophys. 1993, 302 (2): 484–9. PMID 8489250. doi:10.1006/abbi.1993.1243. 
  • Aikawa J, Ikeda-Naiki S, Ohgane J; 等. Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy. Biochim. Biophys. Acta. 1997, 1353 (3): 266–76. PMID 9349722. 
  • Hinds MG, Maurer T, Zhang JG; 等. Solution structure of leukemia inhibitory factor. J. Biol. Chem. 1998, 273 (22): 13738–45. PMID 9593715. doi:10.1074/jbc.273.22.13738. 
  • Toward a complete human genome sequence. Genome Res. 1999, 8 (11): 1097–108. PMID 9847074. doi:10.1101/gr.8.11.1097 (不活跃 2016-12-27). 
  • Tanaka M, Hara T, Copeland NG; 等. Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit. Blood. 1999, 93 (3): 804–15. PMID 9920829. 
  • Nakashima K, Yanagisawa M, Arakawa H; 等. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science. 1999, 284 (5413): 479–82. PMID 10205054. doi:10.1126/science.284.5413.479. 
  • Dunham I, Shimizu N, Roe BA; 等. The DNA sequence of human chromosome 22. Nature. 1999, 402 (6761): 489–95. PMID 10591208. doi:10.1038/990031. 

参见

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白血病抑制因子
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