{
  "abstract": "Microglia, the immune cells of the brain parenchyma, play a pivotal role in neurodevelopment and neuroprotection. Human stem cell-derived microglia-like cells (MGL) offer a valuable, human-relevant system to study microglia in vitro. However, their cell states and intercellular interactions within complex 3-dimensional (3D) tissue contexts in vitro remain underexplored. Here, we analyze the gene expression profiles of MGL generated by two differentiation protocols in conventional 2D cultures. We show that co-culture with neural organoids promotes a more mature, in vivo-like MGL phenotype but this signature is lost during long-term co-culture. By varying media compositions, we modulate 2D MGL states toward more active or more homeostatic identities, which may enhance the similarity to primary microglia identities upon subsequent co-culture. Moreover, forced expression of the microglial lineage regulator SALL1 shifts MGL away from a general myeloid state toward a more defined pre-microglial fate. SALL1 overexpression within a 3D neural organoid environment further amplifies the shift toward a homeostatic developmental microglia population. Collectively, our transcriptomic analysis delineates human MGL states in 2D and 3D contexts, refines existing differentiation protocols toward more authentic MGL, and establishes a framework to investigate the intricate microglia-neural tissue interplay.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biosystems Science and Engineering, ETH Zuerich, Basel, Switzerland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "M. T. Nikolova"
    },
    {
      "name": "K. Freitag"
    },
    {
      "name": "R. Okamoto"
    },
    {
      "name": "A. Catellani"
    },
    {
      "name": "J. Hinke"
    },
    {
      "name": "N. A. Luginbuehl"
    },
    {
      "name": "H.-C. Lin"
    },
    {
      "name": "J. Kaindl"
    },
    {
      "name": "Z. He"
    },
    {
      "name": "P. Wahle"
    },
    {
      "name": "J. Rohland"
    },
    {
      "name": "L. Geirsdottir"
    },
    {
      "name": "J. G. Camp"
    },
    {
      "name": "B. Winner"
    },
    {
      "name": "I. Amit"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Treutlein"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0k3zrbfqq0xja.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754357",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754357v1.full",
  "id": "0k3zrbfqq0xja",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754357v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "developmental biology"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7203759556",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754357v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0k3zrbfqq0xja.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:50Z",
      "native_id": "10.64898/2026.09.25.754357",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754357v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:developmental biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "SALL1 and neural microenvironmental contextspecify identity of stem cell derived humanmicroglia-like cells",
  "title_text": "SALL1 and neural microenvironmental contextspecify identity of stem cell derived humanmicroglia-like cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:50Z",
  "url": "https://research.draconitic.com/paper/0k3zrbfqq0xja",
  "venue": "bioRxiv",
  "versions": []
}