PT  - JOURNAL ARTICLE
AU  - Dorin-Mirel Popescu
AU  - Rachel A. Botting
AU  - Emily Stephenson
AU  - Kile Green
AU  - Laura Jardine
AU  - Emily F. Calderbank
AU  - Mirjana Efremova
AU  - Meghan Acres
AU  - Daniel Maunder
AU  - Peter Vegh
AU  - Issac Goh
AU  - Yorick Gitton
AU  - Jongeun Park
AU  - Krzysztof Polanski
AU  - Roser Vento-Tormo
AU  - Zhichao Miao
AU  - Rachel Rowell
AU  - David McDonald
AU  - James Fletcher
AU  - David Dixon
AU  - Elizabeth Poyner
AU  - Gary Reynolds
AU  - Michael Mather
AU  - Corina Moldovan
AU  - Lira Mamanova
AU  - Frankie Greig
AU  - Matthew Young
AU  - Kerstin Meyer
AU  - Steven Lisgo
AU  - Jaume Bacardit
AU  - Andrew Fuller
AU  - Ben Millar
AU  - Barbara Innes
AU  - Susan Lindsay
AU  - Michael J. T. Stubbington
AU  - Monika S. Kowalczyk
AU  - Bo Li
AU  - Orr Ashenbrg
AU  - Marcin Tabaka
AU  - Danielle Dionne
AU  - Timothy L. Tickle
AU  - Michal Slyper
AU  - Orit Rozenblatt-Rosen
AU  - Andrew Filby
AU  - Alexandra-Chloe Villani
AU  - Anindita Roy
AU  - Aviv Regev
AU  - Alain Chedotal
AU  - Irene Roberts
AU  - Berthold Göttgens
AU  - Elisa Laurenti
AU  - Sam Behjati
AU  - Sarah A. Teichmann
AU  - Muzlifah Haniffa
TI  - Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
AID  - 10.1101/654210
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 654210
4099  - http://biorxiv.org/content/early/2019/05/31/654210.short
4100  - http://biorxiv.org/content/early/2019/05/31/654210.full
AB  - 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.