Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis

Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis
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DOI:
10.1073/pnas.96.13.7526
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发表时间:
1999-06-22
影响因子:
11.1
通讯作者:
Alvarez-Buylla, A
Alvarez-Buylla, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lim, DA;Alvarez-Buylla, A

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哺乳动物心室下区(SVZ)的神经发生贯穿其一生。然而,成人SVZ神经发生所需的信号传导和细胞间相互作用尚不清楚。在体内,迁移的神经母细胞(A型细胞)和假定的前体细胞(C型细胞)与星形胶质细胞(B型细胞)密切接触。B型细胞也会相互接触。我们在无血清或外源性生长因子的培养系统中重建SVZ细胞-细胞相互作用,在星形胶质细胞单层(而不是其他基质)上培养分离的出生后或成年SVZ细胞,支持与体内观察到的相似的广泛神经发生。SVZ前体在星形胶质细胞上迅速增殖,形成包含多达100个A型神经母细胞的集落。通过分离SVZ细胞解离物与固定的聚赖氨酸的不同粘附,我们发现神经元集落形成前体集中在B型和C型细胞富集的部分中。纯A型细胞可以链式迁移,但不能形成神经元集落。由于星形胶质细胞条件培养基本身不足以支持SVZ神经发生,因此星形胶质细胞和SVZ神经元前体之间的直接细胞-细胞接触可能是A型细胞产生的必要条件。
Neurogenesis continues in the mammalian subventricular zone (SVZ) throughout life. However, the signaling and cell-cell interactions required for adult SVZ neurogenesis are not known. In vivo, migratory neuroblasts (type A cells) and putative precursors (type C cells) are in intimate contact with astrocytes (type B cells). Type B cells also contact each other. We reconstituted SVZ cell-cell interactions in a culture system free of serum or exogenous growth factors, Culturing dissociated postnatal or adult SVZ cells on astrocyte monolayers-but not other substrates-supported extensive neurogenesis similar to that observed in vivo. SVZ precursors proliferated rapidly on astrocytes to form colonies containing up to 100 type A neuroblasts. By fractionating the SVZ cell dissociates with differential adhesion to immobilized polylysine, we show that neuronal colony-forming precursors were concentrated in a fraction enriched for type B and C cells. Pure type A cells could migrate in chains but did not give rise to neuronal colonies. Because astrocyte-conditioned medium alone was not sufficient to support SVZ neurogenesis, direct cell-cell contact between astrocytes and SVZ neuronal precursors may be necessary for the production of type A cells.