Postnatal cerebral cortical multipotent progenitors: regulatory mechanisms and potential role in the development of novel neural regenerative strategies.
Postnatal cerebral cortical multipotent progenitors: regulatory mechanisms and potential role in the development of novel neural regenerative strategies.
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出生后大脑皮层多能祖细胞：调节机制和在新型神经再生策略开发中的潜在作用。
DOI：
10.1111/j.1750-3639.1999.tb00539.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Gokhan,S
中科院分区：
文献类型：
--
作者：
Mehler,MF;Gokhan,S
在发育中的大脑皮质中，胶质细胞和神经元的产生时间较长，复杂的中枢神经系统组织的区域微域的功能组织需要局部细胞类型的精确匹配。最近的研究表明，多能祖细胞在神经发生和神经胶质形成过程中发挥着重要作用，这些神经发生和胶质发生是从旁中间生殖区迁移过来的。在严格的局部环境调控下，大脑皮质多能细胞的单独储存库的存在将为损伤后的终末发育塑形和区域细胞池的重建提供适当的机制。我们已经从出生后的哺乳动物大脑皮质中分离出不同的EGF和bFGF反应的多能祖细胞池，独立于脑室下区。这些祖细胞群体受到特定细胞因子亚类的严格环境调控，这些细胞因子亚类规划了中间谱系受限的祖细胞和分化的I型和II型星形胶质细胞、髓鞘少突胶质细胞和表达特定神经调节蛋白的神经元亚型的逐渐细化。这些皮质多能祖细胞的神经谱系发育是一个分级的发育过程，包括特定细胞因子受体的顺序诱导、因子反应性的获得和复杂的谱系相互依赖。皮质多能祖细胞通路规划了具有不同细胞反应特性的神经谱系物种，与来自脑室下区前体细胞的类似物种相比，表明皮质多能细胞有助于在发育中的皮质内建立谱系多样性。此外，皮质多能细胞产生动态的中间祖细胞池，利用时间编码的环境线索来改变神经命运的决定。这些累积的观察结果表明，出生后大脑皮质多能细胞代表了一组新的祖细胞通路，是正常哺乳动物皮质成熟所必需的，可能对我们理解各种神经病理状况以及开发更有效的再生策略来对抗这些普遍存在的神经疾病具有重要意义。
In the developing postnatal cerebral cortex, protracted generation of glia and neurons occurs and precise matching of local cell types is needed for the functional organization of regional microdomains characteristic of complex CNS tissues. Recent studies have suggested that multipotent progenitors play an important role in neural lineage elaboration during neurogenesis and gliogenesis after migration from paramedian generative zones. The presence of a separate reservoir of cerebral cortical multipotent cells under strict local environmental regulation would provide an appropriate mechanism for terminal developmental sculpting and for reconstitution of regional cellular pools after injury. We have isolated distinct pools of EGF‐ and bFGF‐responsive multipotent progenitors from the postnatal mammalian cerebral cortex independent of the subventricular zone. These progenitor populations are under tight environmental regulation by specific hierarchies of cytokine subclasses that program the progressive elaboration of intermediate lineage‐restricted progenitors and differentiated type I and II astrocytes, myelinating oligodendrocytes and neuronal subtypes that express specific neuromodulatory proteins. Neural lineage development from these cortical multipotent progenitors is a graded developmental process involving sequential induction of specific cytokine receptors, acquisition of factor responsiveness and complex lineage interdependence. The cortical multipotent progenitor pathways program the elaboration of neural lineage species with distinct cellular response properties when compared with analogous species derived from subventricular zone progenitors, indicating that the cortical multipotent cells contribute to the establishment of lineage diversity within the developing cortical cortex. In addition, the cortical multipotent cells generate dynamic intermediate progenitor pools that utilize temporally‐coded environmental cues to alter neural fate decisions. These cumulative observations suggest that postnatal cerebral cortical multipotent cells represent a novel set of progenitor pathways necessary for normal mammalian cortical maturation, and may have important implications for our understanding of a wide variety of neuropathological conditions and for the development of more effective regenerative strategies to combat these pervasive neurological disorders.