白血病抑制因子受体信号传导调节神经干细胞的更新。

LIF receptor signaling modulates neural stem cell renewal.

作者信息

Pitman M, Emery B, Binder M, Wang S, Butzkueven H, Kilpatrick T J

机构信息

The Centre for Neuroscience, The University of Melbourne, VIC 3010, Melbourne, Australia.

出版信息

Mol Cell Neurosci. 2004 Nov;27(3):255-66. doi: 10.1016/j.mcn.2004.07.004.

DOI:10.1016/j.mcn.2004.07.004

PMID:15519241

Abstract

Activation of the leukemia inhibitory factor (LIF) receptor has been reported to promote gliogenesis and also to support neural stem cell (NSC) renewal. To investigate this paradox, we isolated NSCs and generated neurospheres from embryonic mice either wild-type, heterozygous, or homozygous null for LIF receptor (LIFR)-beta. Exogenous LIF abrogated neurosphere formation and promoted expression of GFAP by all cells in wild-type and heterozygous cultures. LIF also stimulated a twofold increase in the number of multipotential clones generated from these cultures in comparison with those pretreated with EGF and FGF-2 (E+F) alone. In contrast, the clonogenicity of low-density cultures of LIFR knockout cells was reduced in comparison with that of wild-type cells grown in E+F and was unaffected by LIF. Thus, although LIFR signaling is not necessary for NSC self-renewal, it enhances both the clonogenicity and the expression of GFAP by these multipotential cells.

摘要

据报道，白血病抑制因子（LIF）受体的激活可促进神经胶质细胞生成，也能支持神经干细胞（NSC）的更新。为了研究这一矛盾现象，我们从野生型、杂合型或LIF受体（LIFR）-β基因纯合缺失的胚胎小鼠中分离出神经干细胞并生成神经球。外源性LIF消除了野生型和杂合型培养物中神经球的形成，并促进了所有细胞中GFAP的表达。与仅用表皮生长因子（EGF）和碱性成纤维细胞生长因子-2（FGF-2，即E+F）预处理的培养物相比，LIF还使这些培养物中产生的多能克隆数量增加了两倍。相比之下，与在E+F中生长的野生型细胞相比，LIFR基因敲除细胞的低密度培养物的克隆形成能力降低，且不受LIF影响。因此，虽然LIFR信号传导对于神经干细胞自我更新并非必需，但它可增强这些多能细胞的克隆形成能力和GFAP的表达。