Catunda Ana Paula, Gócza Elen, Carstea Bogdan V, Hiripi Laszlo, Hayes Helene, Rogel-Gaillard Claire, Bertaud Maud, Bosze Zsuzsanna
Agricultural Biotechnology Center, 2100, Szent-Györgyi A. st.4, Gödöllo, Hungary.
Cloning Stem Cells. 2008 Dec;10(4):523-34. doi: 10.1089/clo.2008.0023.
Leukemia inhibitory factor (LIF) is a multifunctional cytokine with an important role during early embryonic development, implantation, and as an inhibitor of murine embryonic stem cell differentiation. It exerts its effects by binding to the leukemia inhibitory factor receptor, a heterodimer of two transmembrane proteins, the specific leukemia inhibitory factor receptor subunit, and the common gp130. A partial cDNA clone coding for the membrane-bound form of the specific rabbit leukemia inhibitory factor receptor was isolated from the genital ridge of 13.5 days postcoitum fetus. Fluorescent in situ hybridization analysis revealed that the rabbit leukemia inhibitory factor receptor gene is located on chromosome OCU11p11.1. It has been shown that the membrane-bound rabbit leukemia inhibitory factor receptor mRNA is expressed during embryo implantation but not at earlier developmental stages. Rabbit embryonic stem cell-like line establishment is improved in the presence of LIF, and those cells express both leukemia inhibitory factor and its receptor. The withdrawal of leukemia inhibitory factor results the differentiation of embryonic stem cell-like cells to beating myocardial-like cells. Our findings suggest that the self-renewal mechanism is similar in mouse and rabbit embryonic stem cells, and expands our knowledge on the role of the LIF-LIFR signal pathway in early rabbit embryogenesis and rabbit embryonic stem cell establishment.
白血病抑制因子(LIF)是一种多功能细胞因子,在早期胚胎发育、着床过程中发挥重要作用,并且是小鼠胚胎干细胞分化的抑制剂。它通过与白血病抑制因子受体结合发挥作用,该受体是由两种跨膜蛋白组成的异二聚体,即特异性白血病抑制因子受体亚基和共同的gp130。从交配后13.5天胎儿的生殖嵴中分离出一个编码特异性兔白血病抑制因子受体膜结合形式的部分cDNA克隆。荧光原位杂交分析表明,兔白血病抑制因子受体基因位于OCU11p11.1染色体上。已表明膜结合的兔白血病抑制因子受体mRNA在胚胎着床期间表达,但在早期发育阶段不表达。在白血病抑制因子存在的情况下,兔胚胎干细胞样系的建立得到改善,并且这些细胞同时表达白血病抑制因子及其受体。去除白血病抑制因子会导致胚胎干细胞样细胞分化为跳动的心肌样细胞。我们的研究结果表明,小鼠和兔胚胎干细胞的自我更新机制相似,并扩展了我们对LIF-LIFR信号通路在早期兔胚胎发生和兔胚胎干细胞建立中的作用的认识。