{
  "abstract": "Current human pluripotent stem cell-derived kidney organoids contain nephron-like structures that lack organotypic patterning. It is thought that during human development, nephrons form their proximal-distal axial polarity in response to collecting duct-derived signals that are absent in kidney organoids. To delineate how nephron polarities establish, we profiled human kidney development by spatial transcriptomic approaches. Our analyses describe a new axial polarity in the nephron and demonstrate that the nephron proximal-distal polarity develops adjacent to a transcriptional boundary in the collecting duct where non-canonical WNT11 is downregulated and canonical WNT9B ligand is upregulated. The nephron region closest to this boundary in turn activates a series of canonical WNT target genes inferring positional nephron identities. To establish whether a canonical WNT source can improve organoid patterning to an in vivo -like state, we bioengineered self-organizing WNT-secreting synthetic organizers. Organizer-coupled kidney organoids respond to WNT ligands by forming expression gradients and developing distal cell identities. Tuning the WNT dose produced nephrons with continuous patterning along the proximal-distal axis. Strikingly, polarized iPSC-derived nephrons directed their distal tubules towards the WNT-source, indicating axial patterning and morphogenetic programs are tuned by WNTs from the synthetic organizers. Our data present a strategy to control organ patterning, build an artificial kidney, and highlights the power of synthetic organizer systems for advancing organoid models.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at University of Southern California, Los Angeles, CA, USA",
    "Maternal Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA",
    "Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA",
    "Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, Los Angeles, CA, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Connor C. Fausto",
      "orcid": "0009-0004-0185-5569"
    },
    {
      "affs": [
        0
      ],
      "name": "Fokion Glykofrydis",
      "orcid": "0000-0002-0865-4573"
    },
    {
      "affs": [
        0
      ],
      "name": "Navneet Kumar",
      "orcid": "0000-0001-5790-3532"
    },
    {
      "affs": [
        0
      ],
      "name": "Jack Schnell",
      "orcid": "0000-0002-6068-5369"
    },
    {
      "affs": [
        0
      ],
      "name": "Réka L. Csipán",
      "orcid": "0009-0000-9306-0608"
    },
    {
      "affs": [
        0
      ],
      "name": "Faith De Kuyper"
    },
    {
      "affs": [
        0
      ],
      "name": "Minnal Kunnan"
    },
    {
      "affs": [
        1
      ],
      "name": "Brendan H. Grubbs",
      "orcid": "0000-0002-1963-4922"
    },
    {
      "affs": [
        1
      ],
      "name": "Matthew Edward Thornton",
      "orcid": "0000-0002-1083-2703"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael Thompson",
      "orcid": "0000-0003-1546-0512"
    },
    {
      "affs": [
        2
      ],
      "name": "Enmian Chang",
      "orcid": "0000-0002-6531-8365"
    },
    {
      "affs": [
        2
      ],
      "name": "Xuduo Wen",
      "orcid": "0000-0002-6363-353X"
    },
    {
      "affs": [
        0
      ],
      "name": "Manuel Pelayo"
    },
    {
      "affs": [
        0
      ],
      "name": "MaryAnne A. Achieng",
      "orcid": "0000-0003-1955-5535"
    },
    {
      "affs": [
        0
      ],
      "name": "Anoothi Seth",
      "orcid": "0009-0009-3872-9802"
    },
    {
      "affs": [
        2
      ],
      "name": "Kelly Street",
      "orcid": "0000-0001-6379-5013"
    },
    {
      "affs": [
        3,
        0
      ],
      "name": "Leonardo Morsut",
      "orcid": "0000-0001-7049-3478"
    },
    {
      "affs": [
        0
      ],
      "name": "Nils O. Lindström",
      "orcid": "0000-0002-7650-2985"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1ywext72e2377.bib",
  "cited_by": 10,
  "doi": "10.1126/science.adu9122",
  "fulltext_url": null,
  "id": "1ywext72e2377",
  "issns": [
    "0036-8075",
    "0193-4511",
    "1095-9203"
  ],
  "landing_url": "https://doi.org/10.1126/science.adu9122",
  "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|Renal and related cancers"
    ]
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  "openalex": "W7167094287",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "42391378",
  "published": "2026-07-02",
  "publisher": "American Association for the Advancement of Science",
  "ris": "https://research.draconitic.com/paper/1ywext72e2377.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W7167094287",
      "source": "openalex",
      "url": "https://doi.org/10.1126/science.adu9122"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Renal and related cancers",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Patterning human kidney organoids with synthetic Wnt-secreting organizers",
  "title_text": "Patterning human kidney organoids with synthetic Wnt-secreting organizers",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/1ywext72e2377",
  "venue": "Science",
  "versions": []
}