Astrocytes and neurons share brain region-specific transcriptional signatures (RNAseq: Astrocytes)

Neuronal cell diversity is essential to endow distinct brain regions with specific functions. During development, progenitors within these regions are characterised by specific gene expression programs, contributing to the generation of diversity in postmitotic neurons and glia. 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 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 glia. 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.

神经元细胞多样性（Neuronal cell diversity）是赋予不同脑区特定功能的关键基础。发育过程中，上述脑区内的祖细胞（progenitors）具有特异性基因表达程序，进而推动有丝分裂后神经元与神经胶质细胞的多样性生成。尽管学界对神经元与星形胶质细胞（astrocytes）的脑区特异性分子多样性的认知日益深入，但此类细胞是否共享脑区特异性程序仍未明确。本研究证实，在新皮层（neocortex）与丘脑（thalamus）中，神经元与星形胶质细胞可表达共享的脑区特异性转录组与表观遗传特征（transcriptional and epigenetic signatures）。这些特征不仅可区分不同脑区的细胞，还能在脑区内的各类亚结构中被检测到——例如不同丘脑核团，克隆分析（clonal analysis）揭示此处存在神经元与神经胶质细胞共有的核团特异性祖细胞。与二者共享的分子特征一致，星形胶质细胞向神经元重编程（astrocyte-to-neuron reprogramming）后，脑区特异性仍得以维持。因此，对这些脑区特异性特征的详尽解析，有望为未来基于细胞的脑修复（cell-based brain repair）策略提供理论指导。