{
  "abstract": "While clinical trials of human pluripotent stem cell-derived midbrain dopamine (mDA) neuron precursor grafts for Parkinson's disease (PD) are ongoing, current protocols remain suboptimal. In particular, the yield of TH+ mDA neurons after in vivo grafting and the expression of certain mDA neuron and subtype-specific markers require improvement. Single-cell transcriptomic analyses of grafts have revealed low proportions of mDA neurons and substantial off-target contamination. Here, we present an optimized mDA neuron differentiation strategy that builds on our clinical-grade (\"Boost\") protocol by adding FGF18 and IWP2 treatment (\"Boost+\") at the neurogenesis stage. Boost+ mDA neurons show higher expression of EN1, PITX3, and ALDH1A1. Improvements in mDA neuron yield and transcriptional similarity to primary mDA neurons are observed in vitro and following transplantation. Single-nucleus RNA sequencing demonstrates enrichment of A9 mDA neurons within Boost+ grafts. Functional studies in vitro demonstrate increased dopamine production and release and improved electrophysiological properties. In vivo analyses show higher percentages of TH+ mDA neurons, resulting in efficient rescue of amphetamine-induced rotation behavior in the 6-OHDA rat model and rescue of deficits in some nondrug-induced assays, including the ladder rung assay, which are not improved by Boost mDA neurons. The Boost+ conditions present an optimized differentiation protocol with advantages for disease modeling and mDA neuron grafting paradigms.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Stem Cell Biology and",
    "Department of Biomedical Science and Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, South Korea",
    "Department of New Biology and",
    "Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA",
    "Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA",
    "Department of Neurosurgery and",
    "Neuroscience program, Graduate School of Medical Sciences, Weill Cornell Medical College, New York, New York, USA",
    "Department of Psychiatry, Columbia University Medical Center, New York, New York, USA",
    "Institute for Computational Biomedicine, Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, New York, USA",
    "Tri-Institutional Ph.D. program in Computational Biology, New York, New York, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "T Kim"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Jinghua Piao",
      "orcid": "0000-0003-1737-911X"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Vittoria Dickinson Bocchi",
      "orcid": "0000-0002-0541-0151"
    },
    {
      "affs": [
        0,
        3,
        6
      ],
      "name": "So Yeon Koo",
      "orcid": "0000-0001-8634-7643"
    },
    {
      "affs": [
        7
      ],
      "name": "Se Joon Choi",
      "orcid": "0009-0002-8229-1704"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Fayzan F. Chaudhry",
      "orcid": "0000-0002-4295-8570"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Donghe Yang",
      "orcid": "0000-0003-1290-4384"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "H Cho"
    },
    {
      "affs": [
        0,
        3,
        6
      ],
      "name": "Emiliano Hergenreder",
      "orcid": "0000-0002-5112-7357"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Lucia Ruiz Perera"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Subhashini Joshi"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Zaki Abou-Mrad",
      "orcid": "0000-0001-6387-8396"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Nidia Claros"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Shkurte Ademi Donohue"
    },
    {
      "affs": [
        1
      ],
      "name": "Yeong Eun Im"
    },
    {
      "affs": [
        1
      ],
      "name": "Hyo Jae Jeong"
    },
    {
      "affs": [
        7
      ],
      "name": "Anika K. Frank",
      "orcid": "0000-0003-4675-2534"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ryan M. Walsh",
      "orcid": "0000-0003-2338-3115"
    },
    {
      "affs": [
        7
      ],
      "name": "Eugene V. Mosharov",
      "orcid": "0000-0002-0229-7114"
    },
    {
      "affs": [
        7
      ],
      "name": "Doron Betel"
    },
    {
      "affs": [
        4,
        0,
        5
      ],
      "name": "Viviane Tabar",
      "orcid": "0000-0002-1284-1670"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Lorenz Studer",
      "orcid": "0000-0003-0741-7987"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ahqc6tqx1f87y.bib",
  "cited_by": 10,
  "doi": "10.1172/jci190954",
  "fulltext_url": null,
  "id": "ahqc6tqx1f87y",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://doi.org/10.1172/jci190954",
  "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": [
    [
      "openalex",
      "1312|Pluripotent Stem Cells Research"
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  "openalex": "W7161419788",
  "pdf_url": null,
  "pmcid": "PMC11741396",
  "pmid": "39829874",
  "published": "2026-05-15",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/ahqc6tqx1f87y.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W7161419788",
      "source": "openalex",
      "url": "https://doi.org/10.1172/jci190954"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Pluripotent Stem Cells Research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Modulation of WNT and FGF18 enhances yield and subtype identity of hPSC-derived midbrain dopamine neurons",
  "title_text": "Modulation of WNT and FGF18 enhances yield and subtype identity of hPSC-derived midbrain dopamine neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/ahqc6tqx1f87y",
  "venue": "Journal of Clinical Investigation",
  "versions": []
}