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神经祖细胞的空间域和新生大鼠脊髓中干细胞龛的功能复杂性。

Spatial domains of progenitor-like cells and functional complexity of a stem cell niche in the neonatal rat spinal cord.

机构信息

Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP11600, Montevideo, Uruguay.

出版信息

Stem Cells. 2012 Sep;30(9):2020-31. doi: 10.1002/stem.1175.

Abstract

During spinal cord development, progenitors in the neural tube are arranged within spatial domains that generate specific cell types. The ependyma of the postnatal spinal cord seems to retain cells with properties of the primitive neural stem cells, some of which are able to react to injury with active proliferation. However, the functional complexity and organization of this stem cell niche in mammals remains poorly understood. Here, we combined immunohistochemistry for cell-specific markers with patch-clamp recordings to test the hypothesis that the ependyma of the neonatal rat spinal cord contains progenitor-like cells functionally segregated within specific domains. Cells on the lateral aspects of the ependyma combined morphological and molecular traits of ependymocytes and radial glia (RG) expressing S100β and vimentin, displayed passive membrane properties and were electrically coupled via Cx43. Cells contacting the ventral and dorsal poles expressed the neural stem cell markers nestin and/or vimentin, had the typical morphology of RG, and appeared uncoupled displaying various combinations of K(+) and Ca(2+) voltage-gated currents. Although progenitor-like cells were mitotically active around the entire ependyma, the proliferative capacity seemed higher on lateral domains. Our findings represent the first evidence that the ependyma of the rat harbors progenitor-like cells with heterogeneous electrophysiological phenotypes organized in spatial domains. The manipulation of specific functional properties in the heterogeneous population of progenitor-like cells contacting the ependyma may in future help to regulate their behavior and lineage potential, providing the cell types required for the endogenous repair of the injured spinal cord.

摘要

在脊髓发育过程中,神经管中的祖细胞排列在产生特定细胞类型的空间域内。出生后脊髓的室管膜似乎保留了具有原始神经干细胞特性的细胞,其中一些细胞能够通过积极增殖对损伤作出反应。然而,哺乳动物中这种干细胞生态位的功能复杂性和组织仍知之甚少。在这里,我们将细胞特异性标志物的免疫组织化学与膜片钳记录相结合,以检验以下假设,即新生大鼠脊髓的室管膜包含在特定区域内功能上分离的祖细胞样细胞。室管膜侧面的细胞结合了表达 S100β 和波形蛋白的室管膜细胞和放射状胶质细胞(RG)的形态和分子特征,表现出被动膜特性,并通过 Cx43 进行电偶联。与腹侧和背侧极接触的细胞表达神经干细胞标志物巢蛋白和/或波形蛋白,具有 RG 的典型形态,并且表现出不偶联,显示出各种 K(+) 和 Ca(2+) 电压门控电流的组合。尽管祖细胞样细胞在整个室管膜周围具有有丝分裂活性,但在侧区的增殖能力似乎更高。我们的发现首次证明大鼠的室管膜含有具有不同电生理表型的祖细胞样细胞,这些细胞组织在空间域中。在与室管膜接触的祖细胞样细胞的异质群体中操纵特定的功能特性,可能有助于调节它们的行为和谱系潜能,为内源性修复损伤的脊髓提供所需的细胞类型。

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