Hematopoiesis during Ontogenesis, Adult Life, and Aging

Abstract

In the bone marrow of vertebrates, two types of stem cells coexist—hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Hematopoiesis only occurs when these two stem cell types and their descendants interact. The descendants of HSCs supply the body with all the mature blood cells, while MSCs give rise to stromal cells that form a niche for HSCs and regulate the process of hematopoiesis. The studies of hematopoiesis were initially based on morphological observations, later extended by the use of physiological methods, and were subsequently augmented by massive application of sophisticated molecular techniques. The combination of these methods produced a wealth of new data on the organization and functional features of hematopoiesis in the ontogenesis of mammals and humans. This review summarizes the current views on hematopoiesis in mice and humans, discusses the development of blood elements and hematopoiesis in the embryo, and describes how the hematopoietic system works in the adult organism and how it changes during aging.

CRLF1 and CLCF1 in Development, Health and Disease

“…Haematopoiesis occurs when these two types of stem cells and their descendants interact. The descendants of HSCs supply the body with all the mature blood cells, while MSCs give rise to stromal cells that form a niche for HSCs and regulate the process of haematopoiesis [123].…”

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

“…Although studies on human hematopoietic ontogeny are much more limited than in murine models, human hematopoiesis is reported to commence at approximately Carnegie Stage (CS) 7–8 of embryonic development (16–18.5 days post-conception (dpc)) in the secondary extra-embryonic yolk sac and in close association with yolk sac endothelial cells, termed the yolk sac blood islands [ 1 , 2 , 3 , 101 , 102 , 103 ]. Based on murine studies, it is generally assumed, although not proven, that human yolk sac-derived hematopoiesis occurs in two waves.…”

“…Based on murine studies, it is generally assumed, although not proven, that human yolk sac-derived hematopoiesis occurs in two waves. The first, or primitive, hematopoietic wave is proposed to generate nucleated erythroid cells, megakaryocytes and macrophages, with the second or pro-definitive hematopoietic wave at around CS13–15 (27–35 dpc) [ 1 , 2 , 3 , 101 , 102 ] generating erythro-myeloid progenitors (EMPs) and potentially certain innate immune or lymphoid-lineage cells from yolk sac hemogenic endothelium (HE) [ 1 , 2 , 3 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ].…”

“…Human development and aging are associated with significant changes in functional hematopoietic cell outputs from specific anatomical regions and hematopoietic tissues [ 1 , 2 , 3 , 4 ]. Importantly, a detailed knowledge of these changes under steady-state and perturbed conditions is critical to understanding hematological disorders and diseases that originate during embryonic, fetal and post-natal life [ 5 , 6 , 7 , 8 , 9 , 10 ].…”

“…From this and other research, the concept of a layered hematopoietic system has emerged [ 2 , 12 , 13 ], with successive, but distinct, waves of hematopoietic stem cell (HSC)-independent hematopoietic progenitor cells (HPCs) originating from the yolk sac and embryo proper prior to the generation of definitive HSCs principally, although not exclusively, from the embryonic para-aortic splanchnopleural/aorta-gonad-mesonephros (P-Sp/AGM) region. Selective HPCs and HSCs then seed the fetal liver, where they mature and expand before HSCs colonize the fetal bone marrow, with bone marrow becoming the main source of HSCs after birth [ 1 , 2 , 3 , 7 ]. Nevertheless, significant challenges still exist in studying HSCs and lineage-restricted HPCs during human embryonic and fetal development and on aging.…”