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Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Author

Listed:
  • Gemma Swiers

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Claudia Baumann

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • John O’Rourke

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Eleni Giannoulatou

    (Computational Biology Research Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Stephen Taylor

    (Computational Biology Research Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Anagha Joshi

    (Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute)

  • Victoria Moignard

    (Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute)

  • Cristina Pina

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Present address: Stem Cell Laboratory, UCL Cancer Institute, University College London, Paul O’Gorman Building, 72 Huntley Street, London WC1E 6BT, UK)

  • Thomas Bee

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

  • Konstantinos D. Kokkaliaris

    (Research Unit Stem Cell Dynamics, Helmholtz Center Munich–German Research Center for Environmental Health
    Present address: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland)

  • Momoko Yoshimoto

    (Wells Center for Pediatric Research, Indiana University School of Medicine)

  • Mervin C. Yoder

    (Wells Center for Pediatric Research, Indiana University School of Medicine)

  • Jon Frampton

    (Institute for Biomedical Research, College of Medical and Dental Sciences, University of Birmingham)

  • Timm Schroeder

    (Research Unit Stem Cell Dynamics, Helmholtz Center Munich–German Research Center for Environmental Health
    Present address: Department of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland)

  • Tariq Enver

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford
    Present address: Stem Cell Laboratory, UCL Cancer Institute, University College London, Paul O’Gorman Building, 72 Huntley Street, London WC1E 6BT, UK)

  • Berthold Göttgens

    (Cambridge Institute for Medical Research and Wellcome Trust & MRC Cambridge Stem Cell Institute)

  • Marella F. T. R. de Bruijn

    (MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford)

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.

Suggested Citation

  • Gemma Swiers & Claudia Baumann & John O’Rourke & Eleni Giannoulatou & Stephen Taylor & Anagha Joshi & Victoria Moignard & Cristina Pina & Thomas Bee & Konstantinos D. Kokkaliaris & Momoko Yoshimoto & , 2013. "Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3924
    DOI: 10.1038/ncomms3924
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    Cited by:

    1. Patrick Coulombe & Grace Cole & Amanda Fentiman & Jeremy D. K. Parker & Eric Yung & Misha Bilenky & Lemlem Degefie & Patrick Lac & Maggie Y. M. Ling & Derek Tam & R. Keith Humphries & Aly Karsan, 2023. "Meis1 establishes the pre-hemogenic endothelial state prior to Runx1 expression," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. C. Biben & T. S. Weber & K. S. Potts & J. Choi & D. C. Miles & A. Carmagnac & T. Sargeant & C. A. Graaf & K. A. Fennell & A. Farley & O. J. Stonehouse & M. A. Dawson & D. J. Hilton & S. H. Naik & S. T, 2023. "In vivo clonal tracking reveals evidence of haemangioblast and haematomesoblast contribution to yolk sac haematopoiesis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Dominic D. G. Owens & Giorgio Anselmi & A. Marieke Oudelaar & Damien J. Downes & Alessandro Cavallo & Joe R. Harman & Ron Schwessinger & Akin Bucakci & Lucas Greder & Sara Ornellas & Danuta Jeziorska , 2022. "Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Zaniah N. Gonzalez Galofre & Alastair M. Kilpatrick & Madalena Marques & Diana Sá da Bandeira & Telma Ventura & Mario Gomez Salazar & Léa Bouilleau & Yvan Marc & Ana B. Barbosa & Fiona Rossi & Mariana, 2024. "Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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