Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming.
Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming.
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DOI：
10.1126/sciadv.abe8978
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发表时间：
2021-04
期刊：
影响因子：
13.6
通讯作者：
López-Bendito G
中科院分区：
文献类型：
--
作者：
Herrero-Navarro Á;Puche-Aroca L;Moreno-Juan V;Sempere-Ferràndez A;Espinosa A;Susín R;Torres-Masjoan L;Leyva-Díaz E;Karow M;Figueres-Oñate M;López-Mascaraque L;López-Atalaya JP;Berninger B;López-Bendito G
与神经元共享的区域特异性基因表达赋予星形胶质细胞进行区域特异性神经元重编程的能力。神经细胞多样性对于赋予不同的大脑区域特定的功能至关重要。在发育过程中，这些区域内的祖细胞具有特定的基因表达程序的特征，有助于有丝分裂后神经元和星形胶质细胞多样性的产生。尽管人们越来越了解神经元和星形胶质细胞的区域特异性分子多样性，但这些细胞是否共享区域特异性程序仍然未知。在这里，我们发现在新皮质和丘脑中，神经元和星形胶质细胞表达共享的区域特异性转录和表观遗传特征。这些特征不仅区分这两个大脑区域的细胞，而且还可以在区域内的子结构中检测到，例如不同的丘脑核，其中克隆分析揭示了神经元和星形胶质细胞共同的核特异性祖细胞的存在。与它们共有的分子特征一致，星形胶质细胞到神经元重编程后仍保持区域特异性。因此，对这些区域特异性特征的详细了解可能会为未来基于细胞的大脑修复策略提供信息。
Region-specific gene expression shared with neurons imparts to astrocytes competence for region-specific neuronal reprogramming. Neural cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterized by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and astrocytes. While the region-specific molecular diversity of neurons and astrocytes is increasingly understood, whether these cells share region-specific programs remains unknown. Here, we show that in the neocortex and thalamus, neurons and astrocytes express shared region-specific transcriptional and epigenetic signatures. These signatures not only distinguish cells across these two brain regions but are also detected across substructures within regions, such as distinct thalamic nuclei, where clonal analysis reveals the existence of common nucleus-specific progenitors for neurons and astrocytes. Consistent with their shared molecular signature, regional specificity is maintained following astrocyte-to-neuron reprogramming. A detailed understanding of these regional-specific signatures may thus inform strategies for future cell-based brain repair.
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影响因子：
23.9
作者：
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通讯作者：
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