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Decoding human fetal liver haematopoiesis

Author

Listed:
  • 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
    European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus)

  • David Dixon

    (Newcastle University)

  • Rachel Rowell

    (Newcastle University)

  • David McDonald

    (Newcastle University)

  • James Fletcher

    (Newcastle University)

  • Elizabeth Poyner

    (Newcastle University
    Newcastle Hospitals NHS Foundation Trust)

  • 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
    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
    Newcastle-upon-Tyne Hospitals NHS Foundation Trust)

  • 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
    Broad Institute of Harvard and MIT)

  • Anindita Roy

    (University of Oxford)

  • Aviv Regev

    (Broad Institute of Harvard and MIT
    Massachusetts Institute of Technology)

  • Alain Chédotal

    (Sorbonne Université, INSERM, CNRS, Institut de la Vision)

  • Irene Roberts

    (University of Oxford
    University of Oxford
    NIHR Oxford Biomedical Centre)

  • Berthold Göttgens

    (University of Cambridge)

  • Sam Behjati

    (Wellcome Genome Campus, Hinxton
    University of Cambridge)

  • Elisa Laurenti

    (University of Cambridge)

  • Sarah A. Teichmann

    (Wellcome Genome Campus, Hinxton
    University of Cambridge)

  • Muzlifah Haniffa

    (Newcastle University
    Wellcome Genome Campus, Hinxton
    Newcastle Hospitals NHS Foundation Trust)

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.

Suggested Citation

  • 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 , 2019. "Decoding human fetal liver haematopoiesis," Nature, Nature, vol. 574(7778), pages 365-371, October.
    • Handle: RePEc:nat:nature:v:574:y:2019:i:7778:d:10.1038_s41586-019-1652-y
    DOI: 10.1038/s41586-019-1652-y
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    Cited by:

    1. Shicheng Sun & Ali Motazedian & Jacky Y. Li & Kevin Wijanarko & Joe Jiang Zhu & Kothila Tharmarajah & Kathleen A. Strumila & Anton Shkaruta & L. Rayburn Nigos & Jacqueline V. Schiesser & Yi Yu & Paul , 2024. "Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Clara Alsinet & Maria Nascimento Primo & Valentina Lorenzi & Erica Bello & Iva Kelava & Carla P. Jones & Roser Vilarrasa-Blasi & Carmen Sancho-Serra & Andrew J. Knights & Jong-Eun Park & Beata S. Wysp, 2022. "Robust temporal map of human in vitro myelopoiesis using single-cell genomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Delilah Hendriks & Benedetta Artegiani & Thanasis Margaritis & Iris Zoutendijk & Susana Chuva de Sousa Lopes & Hans Clevers, 2024. "Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Jake R. Thomas & Anna Appios & Emily F. Calderbank & Nagisa Yoshida & Xiaohui Zhao & Russell S. Hamilton & Ashley Moffett & Andrew Sharkey & Elisa Laurenti & Courtney W. Hanna & Naomi McGovern, 2023. "Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Hanbing Song & Simon Bucher & Katherine Rosenberg & Margaret Tsui & Deviana Burhan & Daniel Hoffman & Soo-Jin Cho & Arun Rangaswami & Marcus Breese & Stanley Leung & María V. Pons Ventura & E. Alejand, 2022. "Single-cell analysis of hepatoblastoma identifies tumor signatures that predict chemotherapy susceptibility using patient-specific tumor spheroids," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Yuan Liao & Lifeng Ma & Qile Guo & Weigao E & Xing Fang & Lei Yang & Fanwei Ruan & Jingjing Wang & Peijing Zhang & Zhongyi Sun & Haide Chen & Zhongliang Lin & Xueyi Wang & Xinru Wang & Huiyu Sun & Xiu, 2022. "Cell landscape of larval and adult Xenopus laevis at single-cell resolution," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Joyce B. Kang & Aparna Nathan & Kathryn Weinand & Fan Zhang & Nghia Millard & Laurie Rumker & D. Branch Moody & Ilya Korsunsky & Soumya Raychaudhuri, 2021. "Efficient and precise single-cell reference atlas mapping with Symphony," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    8. Erica Carolina & Yoshiki Kuse & Ayumu Okumura & Kenji Aoshima & Tomomi Tadokoro & Shinya Matsumoto & Eriko Kanai & Takashi Okumura & Toshiharu Kasai & Souichiro Yamabe & Yuji Nishikawa & Kiyoshi Yamag, 2024. "Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Akimichi Inaba & Zewen Kelvin Tuong & Tian X. Zhao & Andrew P. Stewart & Rebeccah Mathews & Lucy Truman & Rouchelle Sriranjan & Jane Kennet & Kourosh Saeb-Parsy & Linda Wicker & Frank Waldron-Lynch & , 2023. "Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Mingze Gao & Chen Qiao & Yuanhua Huang, 2022. "UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    12. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    13. Ondrej Suchanek & John R. Ferdinand & Zewen K. Tuong & Sathi Wijeyesinghe & Anita Chandra & Ann-Katrin Clauder & Larissa N. Almeida & Simon Clare & Katherine Harcourt & Christopher J. Ward & Rachael B, 2023. "Tissue-resident B cells orchestrate macrophage polarisation and function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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