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Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner

Luis, Tiago C; Barkas, Nikolaos; Carrelha, Joana; Giustacchini, Alice; Mazzi, Stefania; Norfo, Ruggiero; Wu, Bishan; ... Jacobsen, Sten Eirik W; + view all (2019) Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner. Experimental Hematology , 76 (Supp) , Article S77. 10.1016/j.exphem.2019.06.402. Green open access

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Abstract

Hematopoietic stem cells (HSC) are responsible for the on demand production of blood cells both in homeostasis and in response to stress. HSCs reside in specialized niches bone marrow (BM) niches, which regulate their function. These niches are dynamic entities with the capacity to sense and respond to specific requirements in blood production, but the mechanisms underlying this dynamic regulation remain unclear. Accumulating evidence indicate that HSCs are highly heterogeneous, and different BM niches have been proposed, potentially supporting different HSC subsets. We recently identified a subset of HSCs, which is molecularly and functionally primed for platelet replenishment. However, the role of the niche in the regulation of platelet-biased HSC function is still unknown. This work aims at investigating the role of the BM niche in the response of platelet-biased HSCs to thrombocytopenia. In response to platelet depletion platelet-biased HSCs are rapidly and selectively recruited into cell cycle, through a feedback mechanism to replenish platelet numbers and homeostasis. Using RNA-sequencing to analyze different BM niche cell populations and HSC subsets we identified IL-1 as a cytokine released upon platelet depletion and specifically sensed by niche LepR+ perivascular cells. Abrogation of IL-1 signaling specifically in LepR+ niche cells but not in hematopoietic cells impaired the platelet-biased HSC response to platelet depletion. This process was found to be dependent on platelet activation. This work uncovers a molecular mechanism involving the pro-inflammatory signal IL-1 and the niche perivascular cell compartment in the rapid activation of platelet biased HSCs to thrombocytopenia, highlighting a mechanism by which a distinct HSC subset senses and responds to the loss of the lineage it is intrinsically primed for.

Type: Article
Title: Perivascular niche cells sense thrombocytopenia and activate hematopoietic stem cells in an IL-1 dependent manner
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.exphem.2019.06.402
Publisher version: https://doi.org/10.1016/j.exphem.2019.06.402
Language: English
Additional information: Elsevier Open Access License Articles published under an Elsevier user license are Protected by copyright and may be used for non-commercial purposes. Users may access, download, copy, translate, text mine and data mine the articles. https://www.elsevier.com/about/policies-and-standards/open-access-licenses/user
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10177959
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