Haltalli, Myriam L. R. and Watcham, Samuel and Wilson, Nicola K. and Eilers, Kira and Lipien, Alexander and Ang, Heather and Birch, Flora and Anton, Sara Gonzalez and Pirillo, Chiara and Ruivo, Nicola and Vainieri, Maria L. and Pospori, Constandina and Sinden, Robert E. and Luis, Tiago C. and Langhorne, Jean and Duffy, Ken R. and Göttgens, Berthold and Blagborough, Andrew M. and Lo Celso, Cristina (2020) Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection. Nature Cell Biology, 22 (12). pp. 1399-1410. ISSN 1465-7392

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Abstract

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.

Item Type:	Article
Keywords:	Manipulating; niche composition limits damage; haematopoietic stem cells; Plasmodium infection;
Academic Unit:	Faculty of Science and Engineering > Research Institutes > Hamilton Institute
Item ID:	15204
Identification Number:	https://doi.org/10.1038/s41556-020-00601-w
Depositing User:	Dr Ken Duffy
Date Deposited:	10 Jan 2022 13:32
Journal or Publication Title:	Nature Cell Biology
Publisher:	Nature Research
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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