Balancing hematopoietic stem cell self-renewal and differentiation activities throughout ontogeny and aging

During fetal development, lifelong hematopoietic stem cells (HSCs) emerge from hemogenic endothelium as a part of the intra-arterial hematopoietic clusters. These definitive HSCs are deemed to colonize and expand in the fetal liver, migrate to the bone marrow, and produce mature blood cells throughout life. However, emerging lines of evidence have challenged this paradigm, and alternative models have been proposed. Moreover, recent studies have revealed expansion of HSCs during aging, which seems counterintuitive to their age-dependent reduction in regenerative capacity. Here, we summarize emerging views on hematopoietic ontogeny and aging, which was the focus of the Summer 2024 International Society for Experimental Hematology (ISEH) webinar.