{
  "abstract": "Induced pluripotent stem cells (iPSCs) provide a scalable platform for off-the-shelf immune cell therapies; however, the mechanisms controlling maturation and functional specialization of iPSC-derived natural killer (iNK) cells are not fully understood. In this study, we combined single-cell transcriptomics, phenotypic profiling, and functional assays to characterize iNK cells and to determine whether temporally controlled expression of the transcription factor T-BET (TBX21) can promote iNK terminal specification and effector functions. Single-cell RNA sequencing and phenotypic profiling confirmed that baseline iNK cells form a transcriptionally distinct NK population and retain a developmental transcriptional signature. These iNK cells exhibited incomplete terminal maturation compared with peripheral blood NK cells, expressing much of the cytotoxic machinery but displaying limited acquisition of maturation-associated receptors. Despite induction of selected terminal specification markers, T-BET did not shift iNK cells toward a peripheral NK-like transcriptional identity. Instead, T-BET selectively triggered an inflammatory effector program characterized by elevated CCL3 , CCL5 and GZMA expression and increased IFNγ production across multiple tumor targets, without enhancement of terminal cytotoxic gene programs. These findings suggest a functional dissociation between inflammatory and cytotoxic programs in iPSC-derived NK cells. This work highlights transcriptional engineering as a strategy to modulate functional state in stem cell-derived NK cells.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Hematology and Regenerative Medicine, Department of Medicine Huddinge",
    "Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet",
    "Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset",
    "Lund Stem Cell Center and Division of Molecular Hematology, Department of Laboratory Medicine, Lund University",
    "Hematology Center, Karolinska Universitetssjukhuset"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Claire Marsal"
    },
    {
      "affs": [
        0
      ],
      "name": "Muhammad Kashif"
    },
    {
      "affs": [
        0
      ],
      "name": "Sophia Borate"
    },
    {
      "affs": [
        0
      ],
      "name": "Charlotte Hållstrand"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda Haazen"
    },
    {
      "affs": [
        0
      ],
      "name": "Mari Gilljam"
    },
    {
      "affs": [
        0
      ],
      "name": "Yagmur Dölalan"
    },
    {
      "affs": [
        0
      ],
      "name": "Nutsa Burduli"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephan Meinke"
    },
    {
      "affs": [
        0
      ],
      "name": "Anders Norman"
    },
    {
      "affs": [
        0
      ],
      "name": "Alamdar Hussain"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Fredrik Lanner"
    },
    {
      "affs": [
        3
      ],
      "name": "Ewa Sitnicka"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Evren Alici"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2c2e4v8qv6w6p.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1952429",
  "fulltext_url": null,
  "id": "2c2e4v8qv6w6p",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1952429/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune Cell Function and Interaction"
    ]
  ],
  "openalex": "W7223805982",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1952429/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2c2e4v8qv6w6p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1952429",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1952429/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Cell Function and Interaction",
      "subfield": "immunology"
    }
  ],
  "title": "T-BET promotes inflammatory specialization without driving terminal maturation of iPSC-derived NK cells",
  "title_text": "T-BET promotes inflammatory specialization without driving terminal maturation of iPSC-derived NK cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/2c2e4v8qv6w6p",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}