Malaria-induced remodelling of the bone marrow microenvironment mediates loss of haematopoietic stem cell function
| Autor: | Kira Eilers, Alexander Lipien, Robert E. Sinden, Berthold Göttgens, Nicola Ruivo, Heather Ang, Andrew M. Blagborough, Ken R. Duffy, Cristina Lo Celso, Myriam L. R. Haltalli, Nicola K. Wilson, Samuel Watcham, Maria L. Vainieri |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Cell Biology 3. Good health Transplantation 03 medical and health sciences Haematopoiesis 0302 clinical medicine medicine.anatomical_structure Interferon medicine Cancer research Bone marrow Stem cell Progenitor cell Intravital microscopy 030304 developmental biology 030215 immunology medicine.drug |
| DOI: | 10.1101/477190 |
| Popis: | Severe infections are a major source of stress on haematopoiesis, where consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow niches, which have been shown to be altered during ageing and haematopoietic malignancies. Whether the bone marrow (BM) microenvironment plays a role in mediating the effects of infection on HSCs remains an open question. Here we used an murine model of malaria coupled with intravital microscopy, single cell RNA-Seq, mathematical modelling and transplantation assays to obtain a quantitative understanding of the proliferation dynamics of haematopoietic stem and progenitor cells (HSPCs) duringPlasmodiuminfection. We uncovered that duringPlasmodiuminfection the HSC compartment turns over significantly faster than in steady state, and that a global interferon response and loss of functional HSCs are linked to alterations in BM endothelium function and osteoblasts number. Interventions that targeted osteoblasts uncoupled HSC proliferation and function, thus opening up new avenues for therapeutic interventions that may improve the health of survivors of severe infections. |
| Databáze: | OpenAIRE |
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