This session will describe the changes in hematopoietic stem cells (HSC) upon activation due to stress. It will address the metabolic changes that occur in HSC during stress; review how activation of HSC during regenerative stress alters activation and morphology of mitochondria; and highlight how granulocytes and endothelial cells in the bone marrow niche influence activation of HSC during regenerative hematopoiesis.
Dr. Toshio Suda will discuss purine metabolism and the impact of stress on hematopoietic progenitor stem cells. Quiescence and cell division of HSCs are regulated by the dynamic changes in metabolic status as well as in gene expression. Dr. Suda will highlight the role of the adenosine-Ca2+-mitochondria pathway on initiating HSC divisions as well as the role tumor suppressor genes (e.g., folliculin and TFE3) play in metabolic reprogramming and purinergic signaling of hematopoietic cells.
Dr. Marie-Dominique Filippi will demonstrate and discuss the concept of mitochondria driving the loss of HSC stemness after regenerative stress. During bone marrow regeneration, after transplantation, HSC exit quiescence to reconstitute the blood system, which is accompanied by activation of mitochondria and remodeling of their morphology. Mitochondrial morphology is permanently remodeled during and after division and as a result, HSC accumulate dysfunctional mitochondria after stress, thus disrupting the activity of the HSC progeny. Furthermore, irreversible remodeling of mitochondrial morphology also occurs during cumulative division under homeostasis. Using single cell RNAseq and functional assays, Dr. Filippi will show that mitochondria do not return to homeostatic conditions after HSC regeneration because HSC lack proper mitochondrial quality control, namely loss of mitochondrial dynamism.
Dr. Daniel Lucas will discuss recent discoveries in the bidirectional communication between neutrophils and endothelial cells. He will also highlight a critical regulator of emergency and regenerative hematopoiesis and how this regulation impacts the bone marrow niche.
Toshio Suda, MD,PhD
Marie-Dominique Filippi, PhD
Daniel Lucas-Alcaraz, PhD
Active, International, Emeritus, and Honorary Members
Associate, International Associate, Student, and Resident Members