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Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment

2025-12-13Research article Open access
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dc.contributor.authorTeske, Michael
dc.contributor.authorWertheimer, Tobias
dc.contributor.authorButz, Stefan
dc.contributor.authorZwicky, Pascale
dc.contributor.authorMallona, Izaskun
dc.contributor.authorNopper, Svenja L.
dc.contributor.authorMünz, Christian
dc.contributor.authorElling, Ulrich
dc.contributor.authorLancrin, Christophe
dc.contributor.authorBecher, Burkhard
dc.contributor.authorGrosso, Ana Rita
dc.contributor.authorBaubec, Tuncay
dc.contributor.authorSchmolka, Nina
dc.date.accessioned2026-01-09T12:15:37Z
dc.date.available2026-01-09T12:15:37Z
dc.date.issued2025-12-13
dc.description.abstractDuring development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm forming haematopoietic progenitors. This study aims to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employ a murine embryonic stem cell model that recapitulates embryonic blood development, and perform targeted CRISPR-Cas9 knock out screens focusing on transcription factors and chromatin regulators. We identify the transcription factors ETV2, LDB1, SMAD1, SIX4 and ZBTB7b as regulators of haemato-endothelial mesoderm commitment. Embryonic stem cells lacking these regulators give rise to mesodermal subsets with a defined lineage differentiation bias, while transcriptome analysis of these cells uncovers the precise impact of each factor on gene expression in the developing mesoderm. Our study reveals molecular pathways governing mesodermal development crucial to allow endothelial and haematopoietic lineage specification and paves the way for future advances in haematopoietic stem cell applications.eng
dc.identifier.citationTeske, M., Wertheimer, T., Butz, S., & Zwicky, P. et al. (2025). Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment. Nature Communications, 16(1), Article 11412. https://doi.org/10.1038/s41467-025-66230-9
dc.identifier.doi10.1038/s41467-025-66230-9
dc.identifier.eid105025761339
dc.identifier.issn2041-1723
dc.identifier.other746e84ef-6385-4fac-b6af-79be29b62ae0
dc.identifier.pmcPMC12738756
dc.identifier.pmid41390669
dc.identifier.urihttp://hdl.handle.net/10400.14/56462
dc.identifier.wos001647743100005
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleTargeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitmenteng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.titleNature Communications
oaire.citation.volume16
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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