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Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators

Author

Listed:
  • Christian Huisman

    (Oregon Health and Science University)

  • Hyeyoung Cho

    (Oregon Health and Science University)

  • Olivier Brock

    (King’s College London)

  • Su Jeong Lim

    (Soongsil University)

  • Sung Min Youn

    (Soongsil University)

  • Younjung Park

    (Oregon Health and Science University)

  • Sangsoo Kim

    (Soongsil University)

  • Soo-Kyung Lee

    (Oregon Health and Science University
    Oregon Health and Science University)

  • Alessio Delogu

    (King’s College London)

  • Jae W. Lee

    (Oregon Health and Science University
    Department of Biological Sciences, University at Buffalo, Buffalo)

Abstract

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.

Suggested Citation

  • Christian Huisman & Hyeyoung Cho & Olivier Brock & Su Jeong Lim & Sung Min Youn & Younjung Park & Sangsoo Kim & Soo-Kyung Lee & Alessio Delogu & Jae W. Lee, 2019. "Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11667-y
    DOI: 10.1038/s41467-019-11667-y
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    Cited by:

    1. Yi Huang & Anyongqi Wang & Wenjiang Zhou & Baoguo Li & Linshan Zhang & Agata M. Rudolf & Zengguang Jin & Catherine Hambly & Guanlin Wang & John R. Speakman, 2024. "Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Matthew C. Pahl & Claudia A. Doege & Kenyaita M. Hodge & Sheridan H. Littleton & Michelle E. Leonard & Sumei Lu & Rick Rausch & James A. Pippin & Maria Caterina Rosa & Alisha Basak & Jonathan P. Bradf, 2021. "Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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