Decoding human fetal liver haematopoiesis

Dorin-Mirel Popescu, Rachel A. Botting, Emily Stephenson, Kile Green, Simone Webb, Laura Jardine, Emily F. 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 D. Young, Kerstin B. Meyer, Steven Lisgo, Jaume Bacardit, Andrew Fuller, Ben Millar, Barbara Innes, Susan Lindsay, Michael J. T. Stubbington, Monika S. Kowalczyk, Bo Li, Orr Ashenberg, Marcin Tabaka, Danielle Dionne, Timothy L. 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 A. Teichmann () and Muzlifah Haniffa ()
Additional contact information
Dorin-Mirel Popescu: Newcastle University
Rachel A. Botting: Newcastle University
Emily Stephenson: Newcastle University
Kile Green: Newcastle University
Simone Webb: Newcastle University
Laura Jardine: Newcastle University
Emily F. Calderbank: University of Cambridge
Krzysztof Polanski: Wellcome Genome Campus, Hinxton
Issac Goh: Newcastle University
Mirjana Efremova: Wellcome Genome Campus, Hinxton
Meghan Acres: Newcastle University
Daniel Maunder: Newcastle University
Peter Vegh: Newcastle University
Yorick Gitton: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Jong-Eun Park: Wellcome Genome Campus, Hinxton
Roser Vento-Tormo: Wellcome Genome Campus, Hinxton
Zhichao Miao: Wellcome Genome Campus, Hinxton
David Dixon: Newcastle University
Rachel Rowell: Newcastle University
David McDonald: Newcastle University
James Fletcher: Newcastle University
Elizabeth Poyner: Newcastle University
Gary Reynolds: Newcastle University
Michael Mather: Newcastle University
Corina Moldovan: Newcastle Hospitals NHS Foundation Trust
Lira Mamanova: Wellcome Genome Campus, Hinxton
Frankie Greig: Newcastle University
Matthew D. Young: Wellcome Genome Campus, Hinxton
Kerstin B. Meyer: Wellcome Genome Campus, Hinxton
Steven Lisgo: Newcastle University
Jaume Bacardit: School of Computing, Newcastle University
Andrew Fuller: Newcastle University
Ben Millar: Newcastle University
Barbara Innes: Newcastle University
Susan Lindsay: Newcastle University
Michael J. T. Stubbington: Wellcome Genome Campus, Hinxton
Monika S. Kowalczyk: Broad Institute of Harvard and MIT
Bo Li: Broad Institute of Harvard and MIT
Orr Ashenberg: Broad Institute of Harvard and MIT
Marcin Tabaka: Broad Institute of Harvard and MIT
Danielle Dionne: Broad Institute of Harvard and MIT
Timothy L. Tickle: Broad Institute of Harvard and MIT
Michal Slyper: Broad Institute of Harvard and MIT
Orit Rozenblatt-Rosen: Broad Institute of Harvard and MIT
Andrew Filby: Newcastle University
Peter Carey: Broad Institute of Harvard and MIT
Alexandra-Chloé Villani: Massachusetts General Hospital
Anindita Roy: University of Oxford
Aviv Regev: Broad Institute of Harvard and MIT
Alain Chédotal: Sorbonne Université, INSERM, CNRS, Institut de la Vision
Irene Roberts: University of Oxford
Berthold Göttgens: University of Cambridge
Sam Behjati: Wellcome Genome Campus, Hinxton
Elisa Laurenti: University of Cambridge
Sarah A. Teichmann: Wellcome Genome Campus, Hinxton
Muzlifah Haniffa: Newcastle University

Nature, 2019, vol. 574, issue 7778, 365-371

Abstract: Abstract Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 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 influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, 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 reference for harnessing the therapeutic potential of HSC/MPPs.

Date: 2019
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DOI: 10.1038/s41586-019-1652-y

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