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Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level.
Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D; Yoshimoto, Momoko; Yoder, Mervin C; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F T R.
Afiliação
  • Swiers G; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Baumann C; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • O'Rourke J; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Giannoulatou E; Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Taylor S; Computational Biology Research Group, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Joshi A; Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute, Cambridge CB2 OXY, UK.
  • Moignard V; Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute, Cambridge CB2 OXY, UK.
  • Pina C; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Bee T; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Kokkaliaris KD; Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Ingolstaedter Landstrasse 1 85764 Neuherberg, Germany.
  • Yoshimoto M; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
  • Yoder MC; Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
  • Frampton J; Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
  • Schroeder T; Research Unit Stem Cell Dynamics, Helmholtz Center Munich-German Research Center for Environmental Health, Ingolstaedter Landstrasse 1 85764 Neuherberg, Germany.
  • Enver T; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
  • Göttgens B; Department of Haematology, Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute, Cambridge CB2 OXY, UK.
  • de Bruijn MFTR; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Nat Commun ; 4: 2924, 2013.
Article em En | MEDLINE | ID: mdl-24326267
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Embrião de Mamíferos / Hemangioblastos / Análise de Célula Única Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2013 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação da Expressão Gênica no Desenvolvimento / Embrião de Mamíferos / Hemangioblastos / Análise de Célula Única Limite: Animals / Pregnancy Idioma: En Ano de publicação: 2013 Tipo de documento: Article