Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Germany.
Glia. 2011 Jun;59(6):869-81. doi: 10.1002/glia.21156. Epub 2011 Mar 28.
The adult brain parenchyma contains a widespread population of progenitors generating different cells of the oligodendrocyte lineage such as NG2+ cells and some mature oligodendrocytes. However, it is still largely unknown how proliferation and lineage decisions of these progenitors are regulated. Here, we first characterized the cell cycle length, proliferative fraction, and progeny of dividing cells in the adult cerebral cortex and then compared these proliferation characteristics after two distinct stimuli, invasive acute brain injury and increased physiological activity by voluntary physical exercise. Our data show that adult parenchymal progenitors have a very long cell cycle due to an extended G1 phase, many of them can divide at least twice and only a limited proportion of the progeny differentiates into mature oligodendrocytes. After stab wound injury, however, many of these progenitors re-enter the cell cycle very fast, suggesting that the normally long G1 phase is subject to regulation and can be abruptly shortened. In striking contrast, voluntary physical exercise shows the opposite effect with increased exit of the cell cycle followed by an enhanced and fast differentiation into mature oligodendrocytes. Taken together, our data demonstrate that the endogenous population of adult brain parenchymal progenitors is subject to profound modulation by environmental stimuli in both directions, either faster proliferation or faster differentiation.
成人脑实质包含广泛的祖细胞群体，这些祖细胞产生少突胶质细胞谱系的不同细胞，如 NG2+ 细胞和一些成熟的少突胶质细胞。然而，这些祖细胞的增殖和谱系决定如何受到调节仍然很大程度上未知。在这里，我们首先描述了成年大脑皮层中细胞周期长度、增殖分数和分裂细胞的后代，然后比较了两种不同刺激（侵袭性急性脑损伤和自愿体育锻炼增加生理活动）后的这些增殖特征。我们的数据表明，由于 G1 期延长，成年实质祖细胞的细胞周期非常长，其中许多细胞至少可以分裂两次，只有有限比例的后代分化为成熟的少突胶质细胞。然而，在刺伤损伤后，这些祖细胞中的许多细胞很快重新进入细胞周期，这表明正常的长 G1 期受到调节并且可以突然缩短。相比之下，自愿体育锻炼则表现出相反的效果，即细胞周期退出增加，随后快速分化为成熟的少突胶质细胞。总之，我们的数据表明，内源性的成年脑实质祖细胞群体受到环境刺激的深刻调节，可向两个方向发展，即更快的增殖或更快的分化。
