Neuroscience Section, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, OR, 97239, USA.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9RS, UK.
Nat Commun. 2019 Aug 16;10(1):3696. doi: 10.1038/s41467-019-11667-y.
Despite the crucial physiological processes governed by neurons in the hypothalamic arcuate nucleus (ARC), such as growth, reproduction and energy homeostasis, the developmental pathways and regulators for ARC neurons remain understudied. Our single cell RNA-seq analyses of mouse embryonic ARC revealed many cell type-specific markers for developing ARC neurons. These markers include transcription factors whose expression is enriched in specific neuronal types and often depleted in other closely-related neuronal types, raising the possibility that these transcription factors play important roles in the fate commitment or differentiation of specific ARC neuronal types. We validated this idea with the two transcription factors, Foxp2 enriched for Ghrh-neurons and Sox14 enriched for Kisspeptin-neurons, using Foxp2- and Sox14-deficient mouse models. Taken together, our single cell transcriptome analyses for the developing ARC uncovered a panel of transcription factors that are likely to form a gene regulatory network to orchestrate fate specification and differentiation of ARC neurons.
尽管下丘脑弓状核 (ARC) 中的神经元控制着生长、繁殖和能量平衡等至关重要的生理过程，但 ARC 神经元的发育途径和调节因子仍未得到充分研究。我们对小鼠胚胎 ARC 的单细胞 RNA-seq 分析揭示了许多发育中的 ARC 神经元特有的细胞类型标志物。这些标记物包括转录因子，其表达在特定神经元类型中富集，而在其他密切相关的神经元类型中常常耗尽，这表明这些转录因子在特定 ARC 神经元类型的命运决定或分化中发挥重要作用。我们使用 Foxp2 缺陷型和 Sox14 缺陷型小鼠模型，验证了这两个转录因子（Foxp2 富集在 Ghrh 神经元中，Sox14 富集在 Kisspeptin 神经元中）的想法。总之，我们对发育中的 ARC 的单细胞转录组分析揭示了一组转录因子，它们可能形成一个基因调控网络，协调 ARC 神经元的命运决定和分化。
