Department of Molecular Embryology, Max Planck Institute of Immunobiology, Stubeweg 51, Freiburg D-79108, Germany.
Nat Commun. 2012 Feb 14;3:670. doi: 10.1038/ncomms1670.
Neural stem/progenitor cells generate neurons in the adult hippocampus. Neural stem cells produce transient intermediate progenitors (type-2 cells), which generate neuroblasts (type-3 cells) that exit the cell cycle, and differentiate into neurons. The precise dynamics of neuron production from the neural stem cells remains controversial. Here we lineage trace Notch-dependent neural stem cells in the dentate gyrus and show that over 7-21 days, the progeny of the neural stem cells progress through an Ascl1(high) intermediate stage (type-2a) to neuroblasts. However, contrary to predictions, this Ascl1(high) population is not an amplifying intermediate, but it differentiates into mitotic Tbr2(+) early neuroblasts, which in turn expand the lineage. After 100 days, the majority of the neural stem cell progeny are neuroblasts or postmitotic neurons. Hence, the neural stem cells require many weeks to generate differentiated neurons. On the basis of this temporal delay in differentiation and population expansion, we propose that the neural stem cell and early neuroblast divisions drive dentate gyrus neurogenesis and not the amplification of type-2a intermediate progenitors as was previously thought.
神经干细胞/祖细胞在成年海马体中产生神经元。神经干细胞产生短暂的中间祖细胞（type-2 细胞），这些中间祖细胞产生神经母细胞（type-3 细胞），然后退出细胞周期并分化为神经元。神经干细胞产生神经元的确切动力学仍存在争议。在这里，我们对齿状回中的 Notch 依赖性神经干细胞进行谱系追踪，并表明在 7-21 天内，神经干细胞的后代通过 Ascl1(high)中间阶段（type-2a）进展为神经母细胞。然而，与预测相反，这个 Ascl1(high)群体不是扩增中间阶段，而是分化为有丝分裂 Tbr2(+)早期神经母细胞，后者反过来又扩大了谱系。100 天后，大多数神经干细胞后代是神经母细胞或有丝分裂后神经元。因此，神经干细胞需要数周时间才能产生分化的神经元。基于这种分化和群体扩张的时间延迟，我们提出神经干细胞和早期神经母细胞分裂驱动齿状回神经发生，而不是以前认为的 type-2a 中间祖细胞的扩增。
