Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging

Abstract

The past five decades have seen significant progress in our understanding of human hematopoiesis. This has in part been due to the unprecedented development of advanced technologies, which have allowed the identification and characterization of rare subsets of human hematopoietic stem and progenitor cells and their lineage trajectories from embryonic through to adult life. Additionally, surrogate in vitro and in vivo models, although not fully recapitulating human hematopoiesis, have spurred on these scientific advances. These approaches have heightened our knowledge of hematological disorders and diseases and have led to their improved diagnosis and therapies. Here, we review human hematopoiesis at each end of the age spectrum, during embryonic and fetal development and on aging, providing exemplars of recent progress in deciphering the increasingly complex cellular and molecular hematopoietic landscapes in health and disease. This review concludes by highlighting links between chronic inflammation and metabolic and epigenetic changes associated with aging and in the development of clonal hematopoiesis.

Hematopoietic Stem Cells and the Immune System in Development and Aging

“…Clonal haematopoiesis increases risk of malignant blood transformations, age-related diseases, including cardiovascular disease, cancer, and the risk of all-cause mortality [ 18 , 156 , 158 , 163 ]. Recent studies identify specific CHIP-mutations that cause clonal haematopoiesis and, consequently, a high risk of malignant blood transformations.…”

“…As a result, individual HSC clones invade haematopoiesis, narrow the cellular repertoire, leading to anaemia and immunodeficiencies. The proliferation and accumulation of individual hematopoietic clones increases the risk of cardiovascular disease and by accumulation of additional carcinogenic mutations leading to proliferative blood diseases, affecting health and reducing life expectancy [ 18 ].…”

“…Given this focus, we do not discuss in detail other specialized aspects of hematopoietic development. We invite readers to refer to other recent, excellent reviews on specialized topics on HSC hematopoietic hierarchy, function, physiology, and aging [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”