{
  "abstract": "The arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) are highly specialized hypothalamic nuclei controlling appetite and energy expenditure. Here, we demonstrate that human VMH and ARC neurons can be generated from pluripotent stem cells by fine-tuned timing and duration of bone morphogenetic protein (BMP) exposure. We identified SHH − /NKX2.1 + /FGF10 + /RAX + /TBX3 + posterior tuberal progenitors as the source of ARC cell types, including agouti-related peptide (AGRP)-, prepronociceptin (PNOC)-, growth-hormone-releasing hormone (GHRH)-, and thyrotropin-releasing hormone (TRH)-expressing neurons and β2-tanycytes. Differentiated ARC cultures showed high transcriptomic similarity to human ARC and responded to energy homeostasis-regulatory peptides including leptin, glucagon-like peptide 1 (GLP-1), ghrelin, and fibroblast growth factor 1 (FGF1). In contrast, anterior tuberal TBX3 − progenitors generated VMH-associated neurons expressing NR5A1, SOX14 , and GPR149 . Strikingly, two transcriptionally distinct pro-opiomelanocortin (POMC) subpopulations emerged from these lineages, mapping spatially to either the ARC (POMC + /TBX3 + /NR5A2 + ) or the VMH (POMC + /SOX14 + /NR5A1 + ). This model provides a cellular platform to study human hypothalamic subtype specification and pathways involved in central appetite regulation.",
  "abstract_shown": true,
  "affiliations": [
    "Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark",
    "Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark",
    "Department of Experimental Medical Sciences, Wallenberg Centre for Molecular Medicine (WCMM) and Lund Stem Cell Centre, Lund University, 221 84 Lund, Sweden",
    "School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK",
    "Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: agnete.kirkeby@sund.ku.dk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zehra Abay-Nørgaard",
      "orcid": "0000-0002-1366-1751"
    },
    {
      "affs": [
        0
      ],
      "name": "Anika K. Mueller",
      "orcid": "0000-0003-0024-0613"
    },
    {
      "affs": [
        0
      ],
      "name": "Erno Hänninen"
    },
    {
      "affs": [
        1
      ],
      "name": "Dylan M. Belmont-Rausch"
    },
    {
      "affs": [
        0
      ],
      "name": "Louise Piilgaard",
      "orcid": "0000-0003-4585-5996"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucía Sena Trujillo"
    },
    {
      "affs": [
        0
      ],
      "name": "L. Fedrizzi",
      "orcid": "0000-0002-1218-2011"
    },
    {
      "affs": [
        0
      ],
      "name": "Jens Bager Christensen",
      "orcid": "0000-0003-4617-3866"
    },
    {
      "affs": [
        0
      ],
      "name": "Alison Salvador",
      "orcid": "0000-0002-3260-1594"
    },
    {
      "affs": [
        0
      ],
      "name": "Alrik L. Schörling"
    },
    {
      "affs": [
        1
      ],
      "name": "Noah Mottelson"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiuyu Qin"
    },
    {
      "affs": [
        0
      ],
      "name": "Shruthi Sampath"
    },
    {
      "affs": [
        0
      ],
      "name": "Bob Hersbach"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonas Henkenjohann",
      "orcid": "0009-0006-0045-5488"
    },
    {
      "affs": [
        0
      ],
      "name": "Sofie Peeters"
    },
    {
      "affs": [
        2
      ],
      "name": "V.V. Nikulina",
      "orcid": "0000-0002-6255-2148"
    },
    {
      "affs": [
        1
      ],
      "name": "Charlotte Duhn Kruse"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuan Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Kavitha Chinnaiya",
      "orcid": "0000-0002-0760-1795"
    },
    {
      "affs": [
        3
      ],
      "name": "Marysia Placzek",
      "orcid": "0000-0002-4106-9229"
    },
    {
      "affs": [
        0
      ],
      "name": "Janko Kajtez",
      "orcid": "0000-0001-9997-2325"
    },
    {
      "affs": [
        1
      ],
      "name": "Tune H. Pers",
      "orcid": "0000-0003-0207-4831"
    },
    {
      "affs": [
        4
      ],
      "name": "Agnete Kirkeby",
      "orcid": "0000-0001-8203-6901"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/70r5fc03614p8.bib",
  "cited_by": 5,
  "doi": "10.1016/j.stem.2026.05.005",
  "fulltext_url": null,
  "id": "70r5fc03614p8",
  "issns": [
    "1875-9777",
    "1934-5909"
  ],
  "landing_url": "https://doi.org/10.1016/j.stem.2026.05.005",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "2807|Regulation of Appetite and Obesity"
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  "openalex": "W7163876967",
  "pdf_url": null,
  "pmcid": "PMC13353052",
  "pmid": "42259293",
  "published": "2026-06-08",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/70r5fc03614p8.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:11Z",
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      "url": "https://doi.org/10.1016/j.stem.2026.05.005"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2807|Regulation of Appetite and Obesity",
      "subfield": "physiology"
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  ],
  "title": "Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells",
  "title_text": "Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:49Z",
  "url": "https://research.draconitic.com/paper/70r5fc03614p8",
  "venue": "Cell stem cell",
  "versions": []
}