Johe K K, Hazel T G, Muller T, Dugich-Djordjevic M M, McKay R D
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Genes Dev. 1996 Dec 15;10(24):3129-40. doi: 10.1101/gad.10.24.3129.
Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by multipotential CNS stem cells.
识别调控干细胞分化的信号对于理解大脑中的细胞多样性至关重要。在本文中，我们鉴定了以指导性方式发挥作用、引导源自胚胎中枢神经系统（CNS）的多能干细胞分化的因子。中枢神经系统干细胞克隆可分化为多种细胞类型：神经元、星形胶质细胞和少突胶质细胞。克隆中细胞的分化受细胞外信号影响：血小板衍生生长因子（PDGF-AA、-AB和-BB）支持神经元分化。相比之下，睫状神经营养因子和甲状腺激素T3分别对干细胞发挥指导性作用，以生成星形胶质细胞克隆和少突胶质细胞克隆。成体干细胞对这些生长因子的反应非常相似。这些结果支持了一个简单的模型，即通过已知途径短暂暴露于外在因子会引发多能中枢神经系统干细胞的命运决定。
