Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain.

Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain.
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空间转录组学揭示了调节慢性疼痛的小鼠前额叶皮层和神经元亚型的独特组织。

DOI:
10.1038/s41593-023-01455-9
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发表时间:
2023-11
影响因子:
25
通讯作者:
Zhang, Yi
Zhang, Yi
中科院分区:
医学1区
文献类型:
--
作者:
Bhattacherjee, Aritra;Zhang, Chao;Watson, Brianna R.;Djekidel, Mohamed Nadhir;Moffitt, Jeffrey R.;Zhang, Yi

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前额叶皮质(PFC)是一个复杂的大脑区域,它调节着从认知、情绪和执行动作到甚至疼痛处理的各种功能。为了破译这种不同功能的细胞和电路组织,我们采用了成年小鼠PFC的空间分辨单细胞转录组图谱。结果显示,与邻近的皮质区域相比,PFC具有不同的细胞类型组成和基因表达模式,神经元兴奋性调节基因的表达也不同。这些细胞和分子特征在PFC亚区内进一步分离,暗示了几个PFC功能的亚区特异性。PFC通过神经元亚型的组合投射到主要的皮质下靶点,这些亚型以靶点固有的方式出现。最后,基于这些特征,我们确定了慢性疼痛背后的PFC中不同的细胞类型和回路,这是一个分子理解有限的不断升级的医疗挑战。总而言之,这一全面的图谱将有助于解码在健康和疾病中潜在的特定PFC功能的离散的分子、细胞和电路机制。空间转录学揭示了小鼠前额叶皮质(PFC)相对于邻近皮质的不同细胞和电路的组成和组织,这与PFC的不同功能一致,也有助于检测参与慢性疼痛的神经元。
The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and executive action to even pain processing. To decode the cellular and circuit organization of such diverse functions, we employed spatially resolved single-cell transcriptome profiling of the adult mouse PFC. Results revealed that PFC has distinct cell-type composition and gene-expression patterns relative to neighboring cortical areas—with neuronal excitability-regulating genes differently expressed. These cellular and molecular features are further segregated within PFC subregions, alluding to the subregion-specificity of several PFC functions. PFC projects to major subcortical targets through combinations of neuronal subtypes, which emerge in a target-intrinsic fashion. Finally, based on these features, we identified distinct cell types and circuits in PFC underlying chronic pain, an escalating healthcare challenge with limited molecular understanding. Collectively, this comprehensive map will facilitate decoding of discrete molecular, cellular and circuit mechanisms underlying specific PFC functions in health and disease. Spatial transcriptomics reveals distinct composition and organization of cells and circuits in the mouse prefrontal cortex (PFC) relative to adjacent cortices, which concur with PFC’s diverse functions, and also help detect neurons involved in chronic pain.
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