Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection.

Animals Bone Marrow Cells / cytology Endothelial Cells / cytology Gene Expression Profiling / methods Hematopoiesis / drug effects Hematopoietic Stem Cells / cytology Humans Malaria / parasitology Mesenchymal Stem Cells / cytology Mice, Inbred C57BL Mice, Knockout Osteoblasts / cytology Parathyroid Hormone / pharmacology Plasmodium berghei / physiology Reactive Oxygen Species / metabolism Stem Cell Niche / genetics

Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
12 2020
Historique:
received: 03 07 2019
accepted: 06 10 2020
pubmed: 25 11 2020
medline: 23 2 2021
entrez: 24 11 2020
Statut: ppublish

Résumé

Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and combining single-cell RNA sequencing, mathematical modelling, transplantation assays and intravital microscopy, we show that haematopoiesis is reprogrammed upon infection, whereby the HSC compartment turns over substantially faster than at steady-state and HSC function is drastically affected. Interferon is found to affect both haematopoietic and mesenchymal BM cells and we specifically identify a dramatic loss of osteoblasts and alterations in endothelial cell function. Osteo-active parathyroid hormone treatment abolishes infection-triggered HSC proliferation and-coupled with reactive oxygen species quenching-enables partial rescuing of HSC function.

Identifiants

DOI: 10.1038/s41556-020-00601-w PMID: 33230302 PMC: PMC7611033
pubmed: 33230302
doi: 10.1038/s41556-020-00601-w
pii: 10.1038/s41556-020-00601-w
pmc: PMC7611033
mid: EMS126272
doi:

Substances chimiques

Parathyroid Hormone 0
Reactive Oxygen Species 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1399-1410

Subventions

Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206328/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 105398/Z/14/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L023776/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M008975/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 210424/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212304/Z/18/Z
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N00227X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212304
Pays : United Kingdom

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Auteurs

Myriam L R Haltalli (MLR)

Department of Life Sciences, Imperial College London, London, UK.
The Francis Crick Institute, London, UK.
Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Department of Haematology, Cambridge Institute for Medical Research, Cambridge, UK.
ORCID: 0000-0002-0886-4466

Samuel Watcham (S)

Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Department of Haematology, Cambridge Institute for Medical Research, Cambridge, UK.
ORCID: 0000-0002-8399-7875

Nicola K Wilson (NK)

Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Department of Haematology, Cambridge Institute for Medical Research, Cambridge, UK.

Kira Eilers (K)

Department of Life Sciences, Imperial College London, London, UK.

Alexander Lipien (A)

Department of Life Sciences, Imperial College London, London, UK.

Heather Ang (H)

Department of Life Sciences, Imperial College London, London, UK.

Flora Birch (F)

Department of Life Sciences, Imperial College London, London, UK.
The Francis Crick Institute, London, UK.

Sara Gonzalez Anton (SG)

Department of Life Sciences, Imperial College London, London, UK.
The Francis Crick Institute, London, UK.

Chiara Pirillo (C)

Department of Life Sciences, Imperial College London, London, UK.
The Francis Crick Institute, London, UK.

Nicola Ruivo (N)

Department of Life Sciences, Imperial College London, London, UK.

Maria L Vainieri (ML)

Department of Life Sciences, Imperial College London, London, UK.
AO Research Institute, Davos Platz, Switzerland.

Constandina Pospori (C)

Department of Life Sciences, Imperial College London, London, UK.
The Francis Crick Institute, London, UK.

Robert E Sinden (RE)

Department of Life Sciences, Imperial College London, London, UK.

Tiago C Luis (TC)

Department of Life Sciences, Imperial College London, London, UK.
ORCID: 0000-0002-6305-1257

Jean Langhorne (J)

The Francis Crick Institute, London, UK.

Ken R Duffy (KR)

Hamilton Institute, Maynooth University, Maynooth, Ireland.
ORCID: 0000-0001-5587-9356

Berthold Göttgens (B)

Wellcome-Medical Research Council Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
Department of Haematology, Cambridge Institute for Medical Research, Cambridge, UK.
ORCID: 0000-0001-6302-5705

Andrew M Blagborough (AM)

Department of Pathology, University of Cambridge, Cambridge, UK.

Cristina Lo Celso (C)

Department of Life Sciences, Imperial College London, London, UK. c.lo-celso@imperial.ac.uk.
The Francis Crick Institute, London, UK. c.lo-celso@imperial.ac.uk.
ORCID: 0000-0002-1163-4207

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Manipulating niche composition limits damage...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Manipulating niche composition limits damage...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules endothéliales › Manipulating niche composition limits damage...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Manipulating niche composition limits damage...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Manipulating niche composition limits damage...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Manipulating niche composition limits damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Manipulating niche composition limits damage...
questionsmedicales.fr › Infection › Maladies vectorielles › Paludisme › Manipulating niche composition limits damage...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches multipotentes › Cellules souches mésenchymateuses › Manipulating niche composition limits damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Manipulating niche composition limits damage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Manipulating niche composition limits damage...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Ostéoblastes › Manipulating niche composition limits damage...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Hormones peptidiques › Hormone parathyroïdienne › Manipulating niche composition limits damage...
questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Plasmodium berghei › Manipulating niche composition limits damage...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Manipulating niche composition limits damage...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Niche de cellules souches › Manipulating niche composition limits damage...