학술논문
Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection
Document Type
Report
Author
Haltalli, Myriam L.R.; Watcham, Samuel; Wilson, Nicola K.; Eilers, Kira; Lipien, Alexander; Ang, Heather; Birch, Flora; Anton, Sara Gonzales; Pirillo, Chiara; Ruivo, Nicola; Vainieri, Maria L.; Pospori, Constandina; Sinden, Robert E.; Luis, Tiago C.; Langhorne, Jean; Duffy, Ken R.; Gottgens, Berthold; Blagborough, Andrew M.; Celso, Cristina Lo
Source
Nature Cell Biology. December 2020, Vol. 22 Issue 12, p1399, 12 p.
Subject
Language
English
ISSN
1465-7392
Abstract
Author(s): Myriam L. R. Haltalli [sup.1] [sup.2] [sup.3] [sup.4] , Samuel Watcham [sup.3] [sup.4] , Nicola K. Wilson [sup.3] [sup.4] , Kira Eilers [sup.1] , Alexander Lipien [sup.1] , Heather [...]
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. Haltalli et al. show that Plasmodium berghei infection induces interferon release, and affects haematopoietic stem cell proliferation and function, as well as osteoblasts and vascular integrity, in the bone marrow niche.
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. Haltalli et al. show that Plasmodium berghei infection induces interferon release, and affects haematopoietic stem cell proliferation and function, as well as osteoblasts and vascular integrity, in the bone marrow niche.