Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), Minatojima-minamimachi 2-2-3, Chuo-Ku, Kobe 650-0047, Japan.
Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), Minatojima-minamimachi 2-2-3, Chuo-Ku, Kobe 650-0047, Japan CREST (Core Research for Evolutional Science and Technology), Japan Science Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan Laboratory for Development and Regenerative Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe 6500017, Japan
Development. 2015 Feb 1;142(3):431-7. doi: 10.1242/dev.112375. Epub 2015 Jan 6.
The requirement of leukemia inhibitory factor (LIF) for the establishment and maintenance of mouse embryonic stem cells (ESCs) depends on the genetic background of the ESC origin. To reveal the molecular basis of the strain-dependent function of LIF, we compared the activation of the intracellular signaling pathways downstream of LIF in ESCs with different genetic backgrounds. We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from 'permissive' mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was hyperactivated in ESCs from 'non-permissive' strains (NOD, CBA and FVB). Artificial activation of Stat3 supported stable self-renewal of ESCs from non-permissive strains. These data suggest that the difference in the balance between the two intracellular signaling pathways underlies the differential response to LIF.
白血病抑制因子 (LIF) 对于建立和维持小鼠胚胎干细胞 (ESC) 的要求取决于 ESC 起源的遗传背景。为了揭示 LIF 功能的依赖于品系的分子基础，我们比较了具有不同遗传背景的 ESC 中 LIF 下游细胞内信号通路的激活情况。我们发现，在“允许”的小鼠品系（129Sv 和 C57BL6）来源的 ESC 中，JAK-Stat3 通路被显著激活，而在“不允许”的品系（NOD、CBA 和 FVB）来源的 ESC 中，MAP 激酶通路被过度激活。Stat3 的人工激活支持了非允许品系 ESC 的稳定自我更新。这些数据表明，两种细胞内信号通路之间的平衡差异是对 LIF 产生不同反应的基础。
