Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain.

Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain.
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DOI:
10.1371/journal.pone.0018472
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发表时间:
2011-03-31
期刊:
影响因子:
3.7
通讯作者:
Johnson JE
Johnson JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kim EJ;Ables JL;Dickel LK;Eisch AJ;Johnson JE

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Ascl1 (Mash1) 是胚胎发生过程中神经分化所必需的 bHLH 转录因子,但其在成体神经发生中的作用尚不清楚。在这里,我们表明,在成人大脑中,Ascl1 在齿状回颗粒下区 (SGZ) 和更多的头侧室下区 (SVZ) 的神经发生过程中动态表达。具体来说,我们发现 SGZ 1 型细胞和 SVZ B 细胞中 Ascl1 水平较低,但随着细胞过渡到中间祖细胞阶段,Ascl1 水平会增加。使用他莫昔芬 (TAM) 诱导型 Ascl1CreERT2 敲入小鼠品系进行的体内遗传谱系追踪表明,Ascl1 谱系细胞在较长时间内持续产生新的神经元。神经元生成存在区域特异性差异,在出生后第 50 天接受 TAM 的小鼠在 TAM 后 30 天显示出新的齿状回神经元,但甚至在 TAM 后 180 天也显示出新的嗅球神经元。这些结果表明,Ascl1 不仅限于转运放大群体,而且还存在于成人大脑中具有长期神经发生潜力的神经干细胞子集中。
Ascl1 (Mash1) is a bHLH transcription factor essential for neural differentiation during embryogenesis but its role in adult neurogenesis is less clear. Here we show that in the adult brain Ascl1 is dynamically expressed during neurogenesis in the dentate gyrus subgranular zone (SGZ) and more rostral subventricular zone (SVZ). Specifically, we find Ascl1 levels low in SGZ Type-1 cells and SVZ B cells but increasing as the cells transition to intermediate progenitor stages. In vivo genetic lineage tracing with a tamoxifen (TAM) inducible Ascl1CreERT2 knock-in mouse strain shows that Ascl1 lineage cells continuously generate new neurons over extended periods of time. There is a regionally-specific difference in neuron generation, with mice given TAM at postnatal day 50 showing new dentate gyrus neurons through 30 days post-TAM, but showing new olfactory bulb neurons even 180 days post-TAM. These results show that Ascl1 is not restricted to transit amplifying populations but is also found in a subset of neural stem cells with long-term neurogenic potential in the adult brain.
通过确定的因素将成纤维细胞直接转化为功能性神经元。
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