Subependymal Zone-Derived Oligodendroblasts Respond to Focal Demyelination but Fail to Generate Myelin in Young and Aged Mice.
Subependymal Zone-Derived Oligodendroblasts Respond to Focal Demyelination but Fail to Generate Myelin in Young and Aged Mice.
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DOI：
10.1016/j.stemcr.2017.01.007
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发表时间：
2017-03-14
影响因子：
5.9
通讯作者：
Franklin RJM
中科院分区：
文献类型：
--
作者：
Kazanis I;Evans KA;Andreopoulou E;Dimitriou C;Koutsakis C;Karadottir RT;Franklin RJM
成年小鼠胼胝体（CC）内共存两个少突祖细胞群体。局部，实质少突胶质细胞祖细胞（pOPCs）和祖细胞产生于室管膜下区（SEZ）细胞发生生态位。pOPCs在围产期形成，并通过自我更新分裂保持其数量，而sez衍生的细胞相对“年轻”，不断从神经干细胞中诞生。我们比较了这些群体的行为，使用hGFAP:CreErt2小鼠在年轻成人和衰老大脑的稳态和再生CC中标记sez来源的细胞。我们发现，来自经济特区的少突胶质祖细胞具有有限的自我更新潜力，因此不是真正的OPCs，而是“少突胶质母细胞”，更类似于经济特区神经源性输出的神经母细胞。在老年CC中，它们的有丝分裂活性大大降低，尽管它们仍然作为局灶性脱髓鞘的“快速反应元件”。与pOPCs相反，它们在研究的所有年龄都不能产生成熟的髓鞘少突胶质细胞。CC中sez来源的细胞是少突胶质细胞，而不是OPCs少突胶质细胞自我更新能力有限，在脱髓鞘后不能使髓鞘快速反应少突胶质细胞老化不会影响少突胶质细胞与popc的平衡Franklin、Kazanis和同事比较了胼胝体中共存的两种少突胶质细胞形成途径。他们证明，与年龄无关，成体神经干细胞产生少突胶质细胞；即自我更新能力有限的祖细胞对局灶性脱髓鞘反应迅速，但最终不能产生新的髓磷脂，这与驱动髓鞘再生的实质少突胶质祖细胞不同。
Two populations of oligodendrogenic progenitors co-exist within the corpus callosum (CC) of the adult mouse. Local, parenchymal oligodendrocyte progenitor cells (pOPCs) and progenitors generated in the subependymal zone (SEZ) cytogenic niche. pOPCs are committed perinatally and retain their numbers through self-renewing divisions, while SEZ-derived cells are relatively “young,” being constantly born from neural stem cells. We compared the behavior of these populations, labeling SEZ-derived cells using hGFAP:CreErt2 mice, within the homeostatic and regenerating CC of the young-adult and aging brain. We found that SEZ-derived oligodendroglial progenitors have limited self-renewing potential and are therefore not bona fide OPCs but rather “oligodendroblasts” more similar to the neuroblasts of the neurogenic output of the SEZ. In the aged CC their mitotic activity is much reduced, although they still act as a “fast-response element” to focal demyelination. In contrast to pOPCs, they fail to generate mature myelinating oligodendrocytes at all ages studied. SEZ-derived cells in the CC are oligodendroblasts and not OPCs Oligodendroblasts have limited self-renewal capacity and do not make myelin Oligodendroblasts respond rapidly after demyelination Aging does not affect the oligodendroblast-pOPC balance Franklin, Kazanis, and colleagues compare the two oligodendrogenic pathways that co-exist in the corpus callosum. They demonstrate that, irrespective of age, adult neural stem cells generate oligodendroblasts; i.e., progenitors with limited self-renewal capacity that respond rapidly to focal demyelination but eventually fail to generate new myelin, which are different to parenchymal oligodendrocyte progenitor cells that drive remyelination.