The adult mouse hippocampal progenitor is neurogenic but not a stem cell
The adult mouse hippocampal progenitor is neurogenic but not a stem cell
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DOI：
10.1523/jneurosci.3249-05.2005
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发表时间：
2005-11-23
影响因子：
5.3
通讯作者：
Bartlett, PF
中科院分区：
文献类型：
--
作者：
Bull, ND;Bartlett, PF
本研究的目的是表征成年小鼠海马区的增殖前体细胞。鉴于在动物的一生中会产生大量新的海马细胞，预测神经干细胞最终负责维持这种发生。虽然人们普遍认为海马内存在增殖前体，但关于这种细胞的分类存在矛盾的报道。它是真正的干细胞还是更有限的祖细胞？使用一个严格的功能定义的神经干细胞和一些体外试验，我们报告说，居民海马前体是一个祖细胞能够增殖和多能分化，但不能自我更新，从而无限增殖。此外，促分裂剂FGF-2比表皮生长因子（EGF）更大程度地刺激这些细胞的增殖。此外，我们发现BDNF是从海马祖细胞产生神经元所必需的，在增殖过程中需要触发神经元的命运。相反，在海马周围的侧脑室侧壁中发现了真正的神经干细胞。有趣的是，EGF被证明是这种细胞的更强的促有丝分裂因子，这显然是一种与海马祖细胞不同的前体。这些结果表明，最终负责成年海马神经发生的干细胞位于海马体外，产生祖细胞，祖细胞迁移到神经发生区并增殖产生新的神经元和神经胶质。
The aim of this investigation was to characterize the proliferative precursor cells in the adult mouse hippocampal region. Given that a very large number of new hippocampal cells are generated over the lifetime of an animal, it is predicted that a neural stem cell is ultimately responsible for maintaining this genesis. Although it is generally accepted that a proliferative precursor resides within the hippocampus, contradictory reports exist regarding the classification of this cell. Is it a true stem cell or a more limited progenitor? Using a strict functional definition of a neural stem cell and a number of in vitro assays, we report that the resident hippocampal precursor is a progenitor capable of proliferation and multipotential differentiation but is unable to self-renew and thus proliferate indefinitely. Furthermore, the mitogen FGF-2 stimulates proliferation of these cells to a greater extent than epidermal growth factor ( EGF). In addition, we found that BDNF was essential for the production of neurons from the hippocampal progenitor cells, being required during proliferation to trigger neuronal fate. In contrast, a bona fide neural stem cell was identified in the lateral wall of the lateral ventricle surrounding the hippocampus. Interestingly, EGF proved to be the stronger mitogenic factor for this cell, which was clearly a different precursor from the resident hippocampal progenitor. These results suggest that the stem cell ultimately responsible for adult hippocampal neurogenesis resides outside the hippocampus, producing progenitor cells that migrate into the neurogenic zones and proliferate to produce new neurons and glia.