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Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment [SORT-seq]

GSE302880 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2025/10/12 Platform GPL19057
Summary
During development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm generating haematopoietic progenitors. This study aimed to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employed a murine embryonic stem cell model that recapitulates embryonic blood development, and performed targeted CRISPR-Cas9 knock out screens focusing on transcription factors and chromatin regulators, which highlighted the transcription factors Smad1, Ldb1, Six4 and Zbtb7b. Embryonic stem cells lacking these regulators gave rise to mesodermal subsets with a defined lineage differentiation bias, while transcriptome analysis of these cells uncovered the precise impact of each factor on gene expression in the developing mesoderm. Our study reveals novel 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.
Published in
Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitment
Teske M, Wertheimer T, Butz S et al. · Nature communications 2025 · PMID 41390669 · doi:10.1038/s41467-025-66230-9
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Direct links to NCBI, no account and no request form: the whole study as GSE302880_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1292744 and SRA study SRP601494. Searching any of these in the dataset finder brings you back here.

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