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Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
By
Dorin-Mirel Popescu,
Rachel A. Botting,
Emily Stephenson,
Kile Green,
Laura Jardine,
Emily F Calderbank,
Mirjana Efremova,
Meghan Acres,
Daniel Maunder,
Peter Vegh,
Issac Goh,
Yorick Gitton,
Jongeun Park,
Krzysztof Polanski,
Roser Vento-Tormo,
Zhichao Miao,
Rachel Rowell,
David McDonald,
James Fletcher,
David Dixon,
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 J T Stubbington,
Monika S. Kowalczyk,
Bo Li,
Orr Ashenbrg,
Marcin Tabaka,
Danielle Dionne,
Timothy L. Tickle,
Michal Slyper,
Orit Rozenblatt-Rosen,
Andrew Filby,
Alexandra-Chloe Villani,
Anindita Roy,
Aviv Regev,
Alain Chedotal,
Irene Roberts,
Berthold Göttgens,
Elisa Laurenti,
Sam Behjati,
Sarah A Teichmann,
Muzlifah Haniffa
Posted 31 May 2019
bioRxiv DOI: 10.1101/654210
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify the repertoire of blood and immune cells in first and early second trimesters of development. From this data, we infer differentiation trajectories from HSC/MPPs, and evaluate the impact of tissue microenvironment on blood and immune cell development. We predict coupling of mast cell differentiation with erythro-megakaryopoiesis and identify physiological erythropoiesis in fetal skin. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, 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 valuable reference for understanding and harnessing the therapeutic potential of HSC/MPPs.
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