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The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development

Author

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  • Dong Won Kim

    (Johns Hopkins University School of Medicine)

  • Parris Whitney Washington

    (Johns Hopkins University School of Medicine)

  • Zoe Qianyi Wang

    (Johns Hopkins University School of Medicine)

  • Sonia Hao Lin

    (Johns Hopkins University School of Medicine)

  • Changyu Sun

    (Johns Hopkins University School of Medicine)

  • Basma Taleb Ismail

    (Johns Hopkins University School of Medicine)

  • Hong Wang

    (Johns Hopkins University School of Medicine)

  • Lizhi Jiang

    (Johns Hopkins University School of Medicine)

  • Seth Blackshaw

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

Abstract

The hypothalamus is a central regulator of many innate behaviors essential for survival, but the molecular mechanisms controlling hypothalamic patterning and cell fate specification are poorly understood. To identify genes that control hypothalamic development, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across 12 developmental time points between embryonic day 10 and postnatal day 45. This identified genes that delineated clear developmental trajectories for all major hypothalamic cell types, and readily distinguished major regional subdivisions of the developing hypothalamus. By using our developmental dataset, we were able to rapidly annotate previously unidentified clusters from existing scRNA-Seq datasets collected during development and to identify the developmental origins of major neuronal populations of the ventromedial hypothalamus. We further show that our approach can rapidly and comprehensively characterize mutants that have altered hypothalamic patterning, identifying Nkx2.1 as a negative regulator of prethalamic identity. These data serve as a resource for further studies of hypothalamic development, physiology, and dysfunction.

Suggested Citation

  • Dong Won Kim & Parris Whitney Washington & Zoe Qianyi Wang & Sonia Hao Lin & Changyu Sun & Basma Taleb Ismail & Hong Wang & Lizhi Jiang & Seth Blackshaw, 2020. "The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18231-z
    DOI: 10.1038/s41467-020-18231-z
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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. Maja Zupančič & Erik Keimpema & Evgenii O. Tretiakov & Stephanie J. Eder & Itamar Lev & Lukas Englmaier & Pradeep Bhandari & Simone A. Fietz & Wolfgang Härtig & Estelle Renaux & Andreas Villunger & To, 2024. "Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Qiang Liu & Benjamin J. Bell & Dong Won Kim & Sang Soo Lee & Mehmet F. Keles & Qili Liu & Ian D. Blum & Annette A. Wang & Elijah J. Blank & Jiali Xiong & Joseph L. Bedont & Anna J. Chang & Habon Issa , 2023. "A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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