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Decoding human fetal liver haematopoiesis.
Popescu, Dorin-Mirel; Botting, Rachel A; Stephenson, Emily; Green, Kile; Webb, Simone; Jardine, Laura; Calderbank, Emily F; Polanski, Krzysztof; Goh, Issac; Efremova, Mirjana; Acres, Meghan; Maunder, Daniel; Vegh, Peter; Gitton, Yorick; Park, Jong-Eun; Vento-Tormo, Roser; Miao, Zhichao; Dixon, David; Rowell, Rachel; McDonald, David; Fletcher, James; Poyner, Elizabeth; Reynolds, Gary; Mather, Michael; Moldovan, Corina; Mamanova, Lira; Greig, Frankie; Young, Matthew D; Meyer, Kerstin B; Lisgo, Steven; Bacardit, Jaume; Fuller, Andrew; Millar, Ben; Innes, Barbara; Lindsay, Susan; Stubbington, Michael J T; Kowalczyk, Monika S; Li, Bo; Ashenberg, Orr; Tabaka, Marcin; Dionne, Danielle; Tickle, Timothy L; Slyper, Michal; Rozenblatt-Rosen, Orit; Filby, Andrew; Carey, Peter; Villani, Alexandra-Chloé; Roy, Anindita; Regev, Aviv; Chédotal, Alain.
  • Popescu DM; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Botting RA; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Stephenson E; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Green K; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Webb S; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Jardine L; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Calderbank EF; Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
  • Polanski K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Goh I; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Efremova M; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Acres M; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Maunder D; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Vegh P; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Gitton Y; Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.
  • Park JE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Vento-Tormo R; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Miao Z; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Dixon D; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK.
  • Rowell R; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • McDonald D; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Fletcher J; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Poyner E; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Reynolds G; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Mather M; Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Moldovan C; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Mamanova L; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Greig F; Department of Pathology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Young MD; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Meyer KB; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Lisgo S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Bacardit J; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Fuller A; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Millar B; School of Computing, Newcastle University, Newcastle upon Tyne, UK.
  • Innes B; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Lindsay S; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Stubbington MJT; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Kowalczyk MS; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Li B; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
  • Ashenberg O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Tabaka M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Dionne D; Data Sciences Platform, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Tickle TL; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Slyper M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Filby A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Carey P; Haematology Department, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Villani AC; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Roy A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Regev A; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  • Chédotal A; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Nature ; 574(7778): 365-371, 2019 10.
Article en En | MEDLINE | ID: mdl-31597962
ABSTRACT
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Feto / Hematopoyesis / Hígado Límite: Female / Humans Idioma: En Año: 2019 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Feto / Hematopoyesis / Hígado Límite: Female / Humans Idioma: En Año: 2019 Tipo del documento: Article