Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing.

ABSTRACT: Haematopoietic ageing is marked by a loss of regenerative capacity and skewed differentiation from haematopoietic stem cells (HSCs), leading to impaired blood production. Signals from the bone marrow niche tailor blood production, but the contribution of the old niche to haematopoietic ageing remains unclear. Here we characterize the inflammatory milieu that drives both niche and haematopoietic remodelling. We find decreased numbers and functionality of osteoprogenitors at the endosteum and expansion of central marrow LepR⁺ mesenchymal stromal cells associated with deterioration of the sinusoidal vasculature. Together, they create a degraded and inflamed old bone marrow niche. Niche inflammation in turn drives the chronic activation of emergency myelopoiesis pathways in old HSCs

SUBMITTER: Mitchell CA 

PROVIDER: S-EPMC7614279 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature