Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level
| Autor: | Swiers, G, Baumann, C, O'Rourke, J, Giannoulatou, E, Taylor, S, Joshi, A, Moignard, V, Pina, C, Bee, T, Kokkaliaris, K, Yoshimoto, M, Yoder, M, Frampton, J, Schroeder, T, Enver, T, Göttgens, B, De Bruijn, M |
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| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
Male Endothelium Hemangioblasts Transgene Green Fluorescent Proteins General Physics and Astronomy Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Mice Pregnancy medicine Animals Hemogenic endothelium Regulation of gene expression Multidisciplinary Gene Expression Regulation Developmental General Chemistry Embryo Mammalian Cell biology Haematopoiesis medicine.anatomical_structure Enhancer Elements Genetic RUNX1 chemistry Immunology Core Binding Factor Alpha 2 Subunit Female Stem cell Single-Cell Analysis |
| Zdroj: | Nature communications. 4 |
| ISSN: | 2041-1723 |
| Popis: | Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP(+) HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment. |
| Databáze: | OpenAIRE |
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