CRTD-Center for Regenerative Therapies Dresden, Technische Universität Dresden, 01307 Dresden, Germany.
J Neurosci. 2013 Feb 13;33(7):3010-24. doi: 10.1523/JNEUROSCI.3363-12.2013.
Prominin-1 (CD133) is commonly used to isolate stem and progenitor cells from the developing and adult nervous system and to identify cancer stem cells in brain tumors. However, despite extensive characterization of Prominin-1(+) precursor cells from the adult subventricular zone, no information about the expression of Prominin-1 by precursor cells in the subgranular zone (SGZ) of the adult hippocampus has been available. We show here that Prominin-1 is expressed by a significant number of cells in the SGZ of adult mice in vivo and ex vivo, including postmitotic astrocytes. A small subset of Prominin-1(+) cells coexpressed the nonspecific precursor cell marker Nestin as well as GFAP and Sox2. Upon fluorescence-activated cell sorting, only Prominin-1/Nestin double-positive cells fulfilled the defining stem cell criteria of proliferation, self-renewal, and multipotentiality as assessed by a neurosphere assay. In addition, isolated primary Prominin-1(+) cells preferentially migrated to the neurogenic niche in the SGZ upon transplantation in vivo. Finally, despite its expression by various stem and progenitor cells, Prominin-1 turned out to be dispensable for precursor cell proliferation in vitro and in vivo. Nevertheless, a net decrease in hippocampal neurogenesis, by ∼30% was found in Prominin-1 knock-out mice, suggesting other roles in controlling adult hippocampal neurogenesis. Remarkably, an upregulation of Prominin-2 was detected in Prominin-1-deficient mice highlighting a potential compensatory mechanism, which might explain the lack of severe symptoms in individuals carrying mutations in the Prom1 gene.
Prominin-1（CD133）常用于从发育和成年神经系统中分离干细胞和祖细胞，并鉴定脑肿瘤中的癌症干细胞。然而，尽管对成年侧脑室下区的 Prominin-1(+)前体细胞进行了广泛的特征描述，但对于成年海马颗粒下区（SGZ）中前体细胞表达 Prominin-1 的信息却尚未可知。我们在此表明，Prominin-1 在体内和体外成年小鼠的 SGZ 中大量表达，包括有丝分裂后星形胶质细胞。一小部分 Prominin-1(+)细胞共同表达非特异性前体细胞标志物巢蛋白以及 GFAP 和 Sox2。通过荧光激活细胞分选，只有 Prominin-1/Nestin 双阳性细胞满足通过神经球测定评估的增殖、自我更新和多能性的定义干细胞标准。此外，分离的原代 Prominin-1(+)细胞在体内移植后优先迁移到 SGZ 的神经发生龛。最后，尽管 Prominin-1 由各种干细胞和祖细胞表达，但它对于体外和体内前体细胞增殖是可有可无的。尽管如此，在 Prominin-1 敲除小鼠中发现海马神经发生减少了约 30%，这表明它在控制成年海马神经发生方面具有其他作用。值得注意的是，在 Prominin-1 缺陷小鼠中检测到 Prominin-2 的上调，这突显了一种潜在的补偿机制，这可能解释了携带 Prom1 基因突变的个体中缺乏严重症状的原因。
