Glaser Tamara, Opitz Thoralf, Kischlat Thomas, Konang Rachel, Sasse Philipp, Fleischmann Bernd K, Engel Wolfgang, Nayernia Karim, Brüstle Oliver
Institute of Reconstructive Neurobiology, University of Bonn LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany.
Stem Cells. 2008 Sep;26(9):2434-43. doi: 10.1634/stemcells.2008-0163. Epub 2008 Jul 17.
The derivation of autologous pluripotent cells has become a central goal in translational stem cell research. Although somatic cell nuclear transfer and transcription factor-based reprogramming enable the generation of pluripotent cells from adult tissue, both methodologies depend on complex epigenetic alterations. Recent data suggest that the adult germ line may represent an alternative and natural source of pluripotent stem cells. Multipotent adult germ line stem cells (maGSCs) with properties similar to those of embryonic stem cells have been derived from mouse spermatogonial stem cells. These cells exhibit extensive self-renewal, expression of pluripotency markers, and differentiation into derivatives of all three germ layers. Here we report the derivation of multipotent neural and glial precursors as well as adherently proliferating neural stem cells from maGSCs. Characterization of maGSC-derived neurons revealed segregation into GABAergic, glutamatergic, serotonergic, and tyrosine hydroxylase-positive phenotypes. On a functional level, maGSC-derived neurons generate spontaneously active functional networks, which use both glutamatergic and GABAergic synaptic transmission and engage in synchronized oscillatory activity. maGSC-derived oligodendrocytes undergo full maturation and ensheathe host axons in myelin-deficient tissue. Our data suggest that neural stem and precursor cells derived from maGSCs could provide a versatile and potentially autologous source of functional neurons and glia.
自体多能细胞的衍生已成为转化干细胞研究的核心目标。尽管体细胞核移植和基于转录因子的重编程能够从成体组织中生成多能细胞，但这两种方法都依赖于复杂的表观遗传改变。最近的数据表明，成体生殖系可能是多能干细胞的另一种天然来源。具有与胚胎干细胞相似特性的多能成体生殖系干细胞（maGSCs）已从小鼠精原干细胞中获得。这些细胞表现出广泛的自我更新能力、多能性标志物的表达，并能分化为所有三个胚层的衍生物。在此，我们报告了从maGSCs中获得多能神经和神经胶质前体细胞以及贴壁增殖的神经干细胞。对maGSC衍生神经元的表征显示，它们可分为γ-氨基丁酸能、谷氨酸能、5-羟色胺能和酪氨酸羟化酶阳性表型。在功能层面上，maGSC衍生的神经元能形成自发活跃的功能网络，该网络同时利用谷氨酸能和γ-氨基丁酸能突触传递，并参与同步振荡活动。maGSC衍生的少突胶质细胞可完全成熟，并在髓鞘缺乏的组织中包裹宿主轴突。我们的数据表明，源自maGSCs的神经干细胞和前体细胞可能提供一种多功能且潜在的自体功能性神经元和神经胶质来源。
