Decoding human fetal liver haematopoiesis

Dorin-Mirel Popescu (1) , Rachel A Botting (1) , Emily Stephenson (1) , Kile Green (1) , Simone Webb (1) , Laura Jardine (1) , Emily F Calderbank , Krzysztof Polanski (2) , Issac Goh (1) , Mirjana Efremova (2) , Meghan Acres (1) , Daniel Maunder (1) , Peter Vegh (1) , Yorick Gitton (3) , Jong-Eun Park (2) , Roser Vento-Tormo (2) , Zhichao Miao (2) , David Dixon (1) , Rachel Rowell (1) , David Mcdonald (1) , James Fletcher (1) , Elizabeth Poyner (1) , Gary Reynolds (1) , Michael Mather (1) , Corina Moldovan (4) , Lira Mamanova (2) , Frankie Greig (1) , Matthew D Young (2) , Kerstin B Meyer (2) , Steven Lisgo (5) , Jaume Bacardit (6) , Andrew Fuller (1) , Ben Millar (1) , Barbara Innes (1) , Susan Lindsay (5) , Michael J T Stubbington (2) , Monika S Kowalczyk (7) , Bo Li (7) , Orr Ashenberg (7) , Marcin Tabaka (7) , Danielle Dionne (7) , Timothy L Tickle (7) , Michal Slyper (7) , Orit Rozenblatt-Rosen (7) , Andrew Filby (1) , Peter Carey (7) , Alexandra-Chloé Villani (7) , Anindita Roy , Aviv Regev (7) , Alain Chédotal (3) , Irene Roberts (8) , Berthold Göttgens , Sam Behjati (2) , Elisa Laurenti , Sarah A Teichmann (2) , Muzlifah Haniffa (1)

1 Institute of Cellular Medicine [Newcastle]
2 The Wellcome Trust Sanger Institute [Cambridge]
3 Institut de la Vision
4 Newcastle Upon Tyne Hospitals NHS Foundation Trust
5 Institute of Genetic Medicine [Newcastle]
6 School of Computing Science [Newcastle]
7 BROAD INSTITUTE - Broad Institute of MIT and Harvard
8 The Weatherall Institute of Molecular Medicine

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Using single cell transcriptome profiling of ~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 impact of tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, NK and ILC precursors in the yolk sac. 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 harnessing the therapeutic potential of HSC/MPPs.

Mots clés: yolk-sac; kidney; liver; skin; single cell RNA-sequencing; immunology; haematopoiesis; human development

Domaines: Sciences du Vivant [q-bio]

Dorin-Mirel Popescu, Rachel A Botting, Emily Stephenson, Kile Green, Simone Webb, et al.. Decoding human fetal liver haematopoiesis. Nature, 2019, 574, pp.365 - 371. ⟨10.1038/s41586-019-1652-y⟩. ⟨hal-03092615⟩