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

Christian Huisman, Hyeyoung Cho, Olivier Brock, Su Jeong Lim, Sung Min Youn, Younjung Park, Sangsoo Kim, Soo-Kyung Lee, Alessio Delogu () and Jae W. Lee ()
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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
Alessio Delogu: King’s College London
Jae W. Lee: Oregon Health and Science University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11667-y

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