Detalhes bibliográficos
| Resumo: | During 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. |
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| Autores principais: | Teske, Michael |
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| Outros Autores: | Wertheimer, Tobias; Butz, Stefan; Zwicky, Pascale; Mallona, Izaskun; Nopper, Svenja L; Münz, Christian; Elling, Ulrich; Lancrin, Christophe; Becher, Burkhard; Grosso, Ana Rita; Baubec, Tuncay; Schmolka, Nina |
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| Assunto: | Animals Mice CRISPR-Cas Systems/genetics Transcription Factors/genetics Mesoderm/cytology Cell Differentiation/genetics Cell Lineage/genetics Hematopoietic Stem Cells/cytology Gene Expression Regulation, Developmental Mouse Embryonic Stem Cells/cytology Endothelial Cells/cytology Hematopoiesis/genetics General Chemistry General Biochemistry,Genetics and Molecular Biology General Physics and Astronomy |
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| Ano: | 2025 |
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| País: | Portugal |
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| Tipo de documento: | artigo |
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| Tipo de acesso: | acesso aberto |
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| Instituição associada: | Universidade Nova de Lisboa |
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| Idioma: | inglês |
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| Origem: | Repositório Institucional da UNL |
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