The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors.

Autor: Harland LTG; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Simon CS; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.; Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Senft AD; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Costello I; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Greder L; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., Imaz-Rosshandler I; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK., Göttgens B; Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK., Marioni JC; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.; Wellcome Sanger Institute, Cambridge, UK.; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK., Bikoff EK; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Porcher C; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK., de Bruijn MFTR; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK. marella.debruijn@imm.ox.ac.uk., Robertson EJ; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. elizabeth.robertson@path.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2021 Jan; Vol. 23 (1), pp. 61-74. Date of Electronic Publication: 2021 Jan 08.
DOI: 10.1038/s41556-020-00611-8
Abstrakt: Extra-embryonic mesoderm (ExM)-composed of the earliest cells that traverse the primitive streak-gives rise to the endothelium as well as haematopoietic progenitors in the developing yolk sac. How a specific subset of ExM becomes committed to a haematopoietic fate remains unclear. Here we demonstrate using an embryonic stem cell model that transient expression of the T-box transcription factor Eomesodermin (Eomes) governs haemogenic competency of ExM. Eomes regulates the accessibility of enhancers that the transcription factor stem cell leukaemia (SCL) normally utilizes to specify primitive erythrocytes and is essential for the normal development of Runx1 + haemogenic endothelium. Single-cell RNA sequencing suggests that Eomes loss of function profoundly blocks the formation of blood progenitors but not specification of Flk-1 + haematoendothelial progenitors. Our findings place Eomes at the top of the transcriptional hierarchy regulating early blood formation and suggest that haemogenic competence is endowed earlier during embryonic development than was previously appreciated.
Databáze: MEDLINE