Decoding human fetal liver haematopoiesis.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
10 2019
Historique:
received: 26 10 2018
accepted: 09 09 2019
pubmed: 11 10 2019
medline: 28 3 2020
entrez: 11 10 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31597962
doi: 10.1038/s41586-019-1652-y
pii: 10.1038/s41586-019-1652-y
pmc: PMC6861135
mid: EMS84343
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

365-371

Subventions

Organisme : Wellcome Trust
ID : 110104
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R006237/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16040
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00016/13
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12009/14
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107931
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211276
Pays : United Kingdom

Références

Nat Rev Immunol. 2013 Feb;13(2):145-9
pubmed: 23348417
Clin Immunol. 2017 Oct;183:8-16
pubmed: 28645875
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17579-84
pubmed: 23045701
J Clin Immunol. 2013 May;33(4):711-5
pubmed: 23274800
Cell Stem Cell. 2015 Jul 2;17(1):35-46
pubmed: 26095048
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10302-6
pubmed: 7479772
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Immunity. 2014 Sep 18;41(3):465-477
pubmed: 25200712
J Exp Med. 1992 Apr 1;175(4):1055-66
pubmed: 1372642
Blood. 2005 Jun 15;105(12):4715-21
pubmed: 15731180
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):373-8
pubmed: 24344308
Blood. 2019 Aug 1;134(5):480-491
pubmed: 31101625
J Exp Med. 1993 Dec 1;178(6):1857-66
pubmed: 7504051
Nature. 2018 Nov;563(7731):347-353
pubmed: 30429548
Front Immunol. 2017 Sep 20;8:1140
pubmed: 28979259
Development. 2017 Jul 1;144(13):2323-2337
pubmed: 28676567
Pediatr Res. 1995 Jun;37(6):806-11
pubmed: 7544455
J Clin Invest. 2006 Oct;116(10):2808-16
pubmed: 17016561
Nature. 2019 Feb;566(7745):490-495
pubmed: 30787436
Science. 2017 Apr 21;356(6335):
pubmed: 28428369
Science. 2016 Sep 9;353(6304):
pubmed: 27492475
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7629-30
pubmed: 18515423
J Exp Med. 1995 Apr 1;181(4):1445-58
pubmed: 7699329
Front Immunol. 2017 Sep 11;8:1119
pubmed: 28951732
Immunity. 2018 Jun 19;48(6):1160-1171.e5
pubmed: 29858009
Cell Stem Cell. 2013 Oct 3;13(4):459-70
pubmed: 24094326
Nat Methods. 2019 Dec;16(12):1289-1296
pubmed: 31740819
Nat Cell Biol. 2017 Apr;19(4):271-281
pubmed: 28319093
Blood. 2003 Jun 15;101(12):4748-56
pubmed: 12609849
J Exp Med. 1994 Jan 1;179(1):279-90
pubmed: 7505801
Blood. 2015 Apr 16;125(16):2553-7
pubmed: 25755292
Blood. 2014 May 29;123(22):3466-77
pubmed: 24637361
Cell Rep. 2016 Aug 2;16(5):1470-1484
pubmed: 27452463
Nucleic Acids Res. 2019 Jan 8;47(D1):D33-D38
pubmed: 30204897
Annu Rev Immunol. 2016 May 20;34:93-119
pubmed: 26735697
Nat Rev Immunol. 2014 Jun;14(6):392-404
pubmed: 24854589
Cell Stem Cell. 2014 Oct 2;15(4):507-522
pubmed: 25158935
Nature. 2018 Mar 1;555(7694):54-60
pubmed: 29466336
Development. 2013 Jun;140(12):2463-7
pubmed: 23715539
Development. 2015 Sep 15;142(18):3073-6
pubmed: 26395135
Nat Commun. 2018 Oct 5;9(1):4100
pubmed: 30291229
Nature. 2017 Jun 29;546(7660):662-666
pubmed: 28614294
Nat Commun. 2018 Jan 8;9(1):75
pubmed: 29311541
Transfus Med Hemother. 2017 Jun;44(3):143-150
pubmed: 28626365
Obstet Gynecol. 1984 Jan;63(1):26-32
pubmed: 6691014
Cell. 2017 Mar 23;169(1):161-173.e12
pubmed: 28340341
Nat Immunol. 2018 Jul;19(7):711-722
pubmed: 29925996
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Cell Syst. 2019 Apr 24;8(4):281-291.e9
pubmed: 30954476
PLoS Med. 2008 Feb;5(2):e35
pubmed: 18271621
Eur J Immunol. 2017 Aug;47(8):1280-1294
pubmed: 28613415
Immunity. 2018 Sep 18;49(3):464-476.e4
pubmed: 30193847
Nat Commun. 2018 Oct 22;9(1):4383
pubmed: 30348985
Thymus. 1987;10(1-2):45-56
pubmed: 3324404
J Clin Immunol. 2018 Jan;38(1):96-128
pubmed: 29226302
Nat Cell Biol. 2013 Aug;15(8):916-25
pubmed: 23811688
Front Immunol. 2017 Feb 02;8:73
pubmed: 28210260
Annu Rev Immunol. 2017 Apr 26;35:469-499
pubmed: 28226228
Blood. 2016 Mar 10;127(10):1276-86
pubmed: 26773039
Allergy. 2000 Aug;55(8):688-97
pubmed: 10955693
Cell Stem Cell. 2016 Aug 4;19(2):266-277
pubmed: 27345837
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204

Auteurs

Dorin-Mirel Popescu (DM)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Rachel A Botting (RA)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Emily Stephenson (E)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Kile Green (K)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Simone Webb (S)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Laura Jardine (L)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Emily F Calderbank (EF)

Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Krzysztof Polanski (K)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Issac Goh (I)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Mirjana Efremova (M)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Meghan Acres (M)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Daniel Maunder (D)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Peter Vegh (P)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Yorick Gitton (Y)

Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.

Jong-Eun Park (JE)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Roser Vento-Tormo (R)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Zhichao Miao (Z)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, UK.

David Dixon (D)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Rachel Rowell (R)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

David McDonald (D)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

James Fletcher (J)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Elizabeth Poyner (E)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Gary Reynolds (G)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Michael Mather (M)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Corina Moldovan (C)

Department of Pathology, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Lira Mamanova (L)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Frankie Greig (F)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Matthew D Young (MD)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Kerstin B Meyer (KB)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Steven Lisgo (S)

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

Jaume Bacardit (J)

School of Computing, Newcastle University, Newcastle upon Tyne, UK.

Andrew Fuller (A)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Ben Millar (B)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Barbara Innes (B)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Susan Lindsay (S)

Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

Michael J T Stubbington (MJT)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Monika S Kowalczyk (MS)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Bo Li (B)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Data Sciences Platform, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Orr Ashenberg (O)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Marcin Tabaka (M)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Danielle Dionne (D)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Timothy L Tickle (TL)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Haematology Department, Royal Victoria Infirmary, Newcastle-upon-Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Michal Slyper (M)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Orit Rozenblatt-Rosen (O)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Andrew Filby (A)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

Peter Carey (P)

Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Alexandra-Chloé Villani (AC)

Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Data Sciences Platform, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Anindita Roy (A)

Department of Paediatrics, University of Oxford, Oxford, UK.

Aviv Regev (A)

Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Howard Hughes Medical Institute, Koch Institute of Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

Alain Chédotal (A)

Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.

Irene Roberts (I)

Department of Paediatrics, University of Oxford, Oxford, UK.
MRC Molecular Haematology Unit and Department of Paediatrics, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
BRC Blood Theme, NIHR Oxford Biomedical Centre, Oxford, UK.

Berthold Göttgens (B)

Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.

Sam Behjati (S)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. sb31@sanger.ac.uk.
Department of Paediatrics, University of Cambridge, Cambridge, UK. sb31@sanger.ac.uk.

Elisa Laurenti (E)

Department of Haematology and Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK. el422@cam.ac.uk.

Sarah A Teichmann (SA)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. st9@sanger.ac.uk.
Theory of Condensed Matter Group, Cavendish Laboratory/Department of Physics, University of Cambridge, Cambridge, UK. st9@sanger.ac.uk.

Muzlifah Haniffa (M)

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. m.a.haniffa@newcastle.ac.uk.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. m.a.haniffa@newcastle.ac.uk.
Department of Dermatology and NIHR Newcastle Biomedical Research Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. m.a.haniffa@newcastle.ac.uk.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH