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Décodage de l'hématopoïèse fétale hépatique humaine

By Dorin-Mirel Popescu, Rachel Botting, Emily Stephenson, Kile Green, Simone Webb, Laura Jardine, Emily Calderbank, Krzysztof Polanski, Issac Goh, Mirjana Efremova, Meghan Acres, Daniel Maunder, Peter Vegh, Yorick Gitton, Jong-Eun Park, Roser Vento-Tormo, Zhichao Miao, David Dixon, Rachel Rowell, David Mcdonald, James Fletcher, Elizabeth Poyner, Gary Reynolds, Michael Mather, Corina Moldovan, Lira Mamanova, Frankie Greig, Matthew Young, Kerstin Meyer, Steven Lisgo, Jaume Bacardit, Andrew Fuller, Ben Millar, Barbara Innes, Susan Lindsay, Michael Stubbington, Monika Kowalczyk, Bo Li, Orr Ashenberg, Marcin Tabaka, Danielle Dionne, Timothy Tickle, Michal Slyper, Orit Rozenblatt-Rosen, Andrew Filby, Peter Carey, Alexandra-Chloé Villani, Anindita Roy, Aviv Regev, Alain Chédotal, Irene Roberts, Berthold Göttgens, Sam Behjati, Elisa Laurenti, Sarah Teichmann and Muzlifah Haniffa


International audienceDefinitive haematopoiesis in the fetal liver supports self-renewal anddifferentiation of haematopoietic stem cells and multipotent progenitors(HSC/MPPs) but remains poorly defined in humans. Here, using single-celltranscriptome profiling of approximately 140,000 liver and 74,000 skin, kidneyand yolk sac cells, we identify the repertoire of human blood and immune cellsduring development. We infer differentiation trajectories from HSC/MPPs andevaluate the influence of the tissue microenvironment on blood and immune celldevelopment. We reveal physiological erythropoiesis in fetal skin and thepresence of mast cells, natural killer and innate lymphoid cell precursors in theyolk sac. We demonstrate a shift in the haemopoietic composition of fetal liverduring gestation away from being predominantly erythroid, accompanied by aparallel change in differentiation potential of HSC/MPPs, which we functionallyvalidate. Our integrated map of fetal liver haematopoiesis provides a blueprintfor the study of paediatric blood and immune disorders, and a reference forharnessing the therapeutic potential of HSC/MPPs

Topics: [SDV]Life Sciences [q-bio]
Publisher: 'Springer Science and Business Media LLC'
Year: 2019
DOI identifier: 10.1038/s41586-019-1652-y
OAI identifier: oai:HAL:hal-02323941v1
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