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A comprehensive human embryo reference tool using single-cell RNA-sequencing data
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ sjukhuset, Div Obstet & Gynecol, Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ sjukhuset, Div Obstet & Gynecol, Stockholm, Sweden.;Andalusian Mol Biol & Regenerat Med Ctr CABIMER, Dept Regenerat & Cell Therapy, Seville, Spain..
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ sjukhuset, Div Obstet & Gynecol, Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ sjukhuset, Div Obstet & Gynecol, Stockholm, Sweden.;Univ Helsinki, Stem Cells & Metab Res Program, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
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2025 (English)In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 22, no 1, p. 193-206Article in journal (Refereed) Published
Abstract [en]

Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of embryo models hinges on their molecular, cellular and structural fidelities to their in vivo counterparts. To authenticate human embryo models, single-cell RNA sequencing has been utilized for unbiased transcriptional profiling. However, an organized and integrated human single-cell RNA-sequencing dataset, serving as a universal reference for benchmarking human embryo models, remains unavailable. Here we developed such a reference through the integration of six published human datasets covering development from the zygote to the gastrula. Lineage annotations are contrasted and validated with available human and nonhuman primate datasets. Using stabilized Uniform Manifold Approximation and Projection, we constructed an early embryogenesis prediction tool, where query datasets can be projected on the reference and annotated with predicted cell identities. Using this reference tool, we examined published human embryo models, highlighting the risk of misannotation when relevant references are not utilized for benchmarking and authentication. This resource integrates different human embryo datasets to create a transcriptional reference map of human embryonic development from zygote to gastrula.

Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 22, no 1, p. 193-206
National Category
Developmental Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-555271DOI: 10.1038/s41592-024-02493-2ISI: 001354858200001PubMedID: 39543283Scopus ID: 2-s2.0-85209107710OAI: oai:DiVA.org:uu-555271DiVA, id: diva2:1954326
Funder
Swedish Research Council, 2023-02582Swedish Research Council, 2016-01919Swedish Research Council, 2022-06725Vinnova, 2021-02695Swedish Society for Medical Research (SSMF), S16-0039Available from: 2025-04-24 Created: 2025-04-24 Last updated: 2025-04-24Bibliographically approved

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CiteExportLink to record
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