Clonal Identity Determines Astrocyte Cortical Heterogeneity
Clonal Identity Determines Astrocyte Cortical Heterogeneity
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DOI：
10.1093/cercor/bhs134
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发表时间：
2013-06-01
期刊：
影响因子：
3.7
通讯作者：
Lopez-Mascaraque, Laura
中科院分区：
文献类型：
--
作者：
Garcia-Marques, Jorge;Lopez-Mascaraque, Laura
星形胶质细胞是大脑中数量最多的细胞类型，已知它们在其中扮演着多种重要的功能。虽然有越来越多的证据表明它们在形态、分子和功能上的异质性，但尚不清楚它们的位置和形态特征是否在大脑发育过程中被明确规定。我们用一种新的策略来解决这个问题，通过荧光蛋白的组合表达来分析细胞谱系。在子宫电穿孔后，这些蛋白的随机表达产生了可遗传的标记，使得能够在体内长期追踪神经胶质祖细胞谱系。对成体皮质克隆分布的分析揭示了出乎意料的、高度特异的克隆分布模式。除了在特定区域存在克隆排列外，我们还发现不同类别的星形胶质细胞来自不同的克隆。这加强了血统起源影响细胞异质性的观点，揭示了星形胶质细胞多样性的新水平，可能与特定的区域功能有关。
Astrocytes are the most numerous cell type in the brain, where they are known to play multiple important functions. While there is increasing evidence of their morphological, molecular, and functional heterogeneity, it is not clear whether their positional and morphological identities are specified during brain development. We address this problem with a novel strategy to analyze cell lineages through the combinatorial expression of fluorescent proteins. Following in utero electroporation, stochastic expression of these proteins produces inheritable marks that enable the long-term in vivo tracing of glial progenitor lineages. Analyses of clonal dispersion in the adult cortex revealed unanticipated and highly specific clonal distribution patterns. In addition to the existence of clonal arrangements in specific domains, we found that different classes of astrocytes emerge from different clones. This reinforces the view that lineage origin impinges on cell heterogeneity, unveiling a new level of astrocyte diversity likely associated with specific regional functions.