Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
Author:
Popescu Dorin-Mirel, Botting Rachel A., Stephenson Emily, Green Kile, Jardine Laura, Calderbank Emily F., Efremova Mirjana, Acres Meghan, Maunder Daniel, Vegh Peter, Goh Issac, Gitton Yorick, Park Jongeun, Polanski Krzysztof, Vento-Tormo Roser, Miao Zhichao, Rowell Rachel, McDonald David, Fletcher James, Dixon David, Poyner Elizabeth, Reynolds Gary, Mather Michael, Moldovan Corina, Mamanova Lira, Greig Frankie, Young Matthew, Meyer Kerstin, Lisgo Steven, Bacardit Jaume, Fuller Andrew, Millar Ben, Innes Barbara, Lindsay Susan, Stubbington Michael J. T., Kowalczyk Monika S., Li Bo, Ashenbrg Orr, Tabaka Marcin, Dionne Danielle, Tickle Timothy L., Slyper Michal, Rozenblatt-Rosen Orit, Filby Andrew, Villani Alexandra-Chloe, Roy Anindita, Regev Aviv, Chedotal Alain, Roberts Irene, Göttgens Berthold, Laurenti ElisaORCID, Behjati Sam, Teichmann Sarah A., Haniffa Muzlifah
Abstract
SummaryDefinitive 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.
Publisher
Cold Spring Harbor Laboratory
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