{
  "abstract": "Background: Hematopoietic stem cells (HSCs) have the unique ability to produce all mature cell types in the blood and understanding the mechanisms governing their differentiation and renewal is a driving question in stem cell biology. While single-cell RNA sequencing has transformed our view of human hematopoiesis, mRNA abundance represents an incomplete proxy for functional cell states. Here, we apply single-cell multimodal profiling to simultaneously measure 280 surface and intracellular protein targets alongside whole transcriptomes within individual adult human hematopoietic stem and progenitor cells. Results: By directly coupling modalities within single cells, we show that protein-RNA correlations peak dynamically in transitioning intermediate progenitors across lineages, consistent with pervasive post-transcriptional mechanics underlying lineage choice. Furthermore, key transcription factor proteins maintain multilineage co-expression longer into commitment than their transcripts, demarcating a possible window of fate decision reversibility. Moreover, low and flat CTNNB1 mRNA levels mask late-erythroid {beta}-catenin protein enrichment, apparently pairing with E-cadherin expression and suggesting post-translational stabilization at the cell membrane. Conclusions: This dataset enables the observation of translational dynamics and RNA-protein relationships throughout the differentiation landscape at an unprecedented level of granularity. Together, our findings demonstrate that transcriptomics alone misses fundamental regulatory programs, establishing single-cell proteo-transcriptomics as a powerful tool for decoding human stem cell fate.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cambridge"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "J. Gollin"
    },
    {
      "name": "N. Garcia-Gisbert"
    },
    {
      "name": "T. Isobe"
    },
    {
      "name": "E. Laurenti"
    },
    {
      "name": "B. Gottgens"
    },
    {
      "name": "A. Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "N. K. Wilson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bnb26t70vdq95.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.09.757909",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1.full",
  "id": "bnb26t70vdq95",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7221577398",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bnb26t70vdq95.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:20Z",
      "native_id": "10.64898/2026.10.09.757909",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.09.757909v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Single-Cell Proteo-Transcriptomic Profiling Uncovers Post-Translational Regulatory Layers in Human Hematopoiesis",
  "title_text": "Single-Cell Proteo-Transcriptomic Profiling Uncovers Post-Translational Regulatory Layers in Human Hematopoiesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:20Z",
  "url": "https://research.draconitic.com/paper/bnb26t70vdq95",
  "venue": "bioRxiv",
  "versions": []
}