The bone marrow niche landscape:a journey through aging,extrinsic and intrinsic stressors in the haemopoietic milieu

Inflammation and its effects in the bone marrow microenvironment represent a paradigmatic condition in which the hematopoietic niche and the immune systems,thought to properly sustain blood cell production and distinguish between friend and foe,can actively sustain a corrupted neighborhood within a chronic aberrant inflamed state.The bone marrow niche hijacks the physiologic hematopoiesis.The interactions between the hematopoietic stem cells and the niche in the bone marrow are critical determinants of quiescence.We examined several approaches to confront the available evidence;three key points emerged,pointing to the chronic inflammation process,especially the chronic infection and systemic inflammatory states,as leading causes of hematopoietic stem cell depletion.Clonal hematopoiesis,defined as a relative expansion of individual clones,is caused by somatic alterations in essential hematopoietic genes,which increase stem cell fitness.Moreover,terminal differentiation plays a significant role in progenitor loss and inflammatory signaling,promoting clonal selection and clonal hematopoiesis conditions.Specific myeloid malignancies as paradigmatic examples are discussed as a condition associated with inflammation,including the 5q-syndrome,Philadelphia negative myeloproliferative neoplasms,and chronic myeloid leukemia.Aging with increased fitness and hematopoietic stem cell attrition,extrinsic stress,enhanced stressor-specific fitness,and intrinsic defect across the hematopoietic process represent the route for novel insights in defective hematopoiesis.The discussion in this review also points out that the hematopoietic niches’inflammatory stimulation may affect differentiation patterns and the function of downstream cells.