Abstract
All vertebrate blood cells descend from multipotent hematopoietic stem cells (HSCs), whose activity and differentiation depend on a complex and incompletely understood relationship with inflammatory signals. Although homeostatic levels of inflammatory signaling play an intricate role in HSC maintenance, activation, proliferation, and differentiation, acute or chronic exposure to inflammation can have deleterious effects on HSC function and self-renewal capacity, and bias their differentiation program. Increased levels of inflammatory signaling are observed during aging, affecting HSCs either directly or indirectly via the bone marrow niche and contributing to their loss of self-renewal capacity, diminished overall functionality, and myeloid differentiation skewing. These changes can have significant pathological consequences. Here, we provide an overview of the current literature on the complex interplay between HSCs and inflammatory signaling, and how this relationship contributes to age-related phenotypes. Understanding the mechanisms and outcomes of this interaction during different life stages will have significant implications in the modulation and restoration of the hematopoietic system in human disease, recovery from cancer and chemotherapeutic treatments, stem cell transplantation, and aging.
Highlights
The establishment and maintenance of the lifelong supply of blood cells relies on a rare population of multipotent and self-renewing hematopoietic stem cells (HSCs), which reside in specialized niches within the bone marrow (BM) [1]
HSCs are influenced by age-related changes to the BM niche, and especially by the elevated levels of pro-inflammatory cytokines expressed in the aged niche (Figure 2)
Certain levels of inflammation are required for proper HSC development, maintenance, activation, and differentiation, sustained chronic or excessive levels of inflammatory signaling negatively affect the function and self-renewal of HSCs, and bias their differentiation program
Summary
The establishment and maintenance of the lifelong supply of blood cells relies on a rare population of multipotent and self-renewing hematopoietic stem cells (HSCs), which reside in specialized niches within the bone marrow (BM) [1]. Low-grade chronic inflammation has been shown to affect HSC functionality, numbers, and differentiation, but is one of the hallmarks of the aged hematopoietic system [30,31,32]. Excessive exposure to these signals can be a harbinger of HSC exhaustion and functional impairment [33]. Understanding how inflammation affects HSC homeostasis and cell fate decisions can lead to the development of clinical interventions and therapies for maintaining a healthy hematopoietic system after insults, cancer treatments, and aging
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