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.
Highlights
Mesenchymal Cells during EmbryogenesisHematopoietic precursors develop in an ensemble with mesenchymal cells, as evidenced by many findings
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The third wave arises inside the embryo in the region of the aorta–gonad–mesonephros (AGM), and gives rise to adult hematopoiesis, resulting in the formation of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) that provide the organism with continuous production of blood cells [1,2,3,4]
Summary
Hematopoietic precursors develop in an ensemble with mesenchymal cells, as evidenced by many findings. The combination of genetic barcoding and next-generation sequencing (NGS) methods made it possible to determine the most complete clonal composition of the hematopoietic cell population and its dynamics in the hematopoietic system of mice, primates, and humans after transplantation of marked bone marrow cells into an irradiated or appropriately conditioned organism [42,43,44,45,46] These studies confirmed the earlier proposed clonal succession model stating that many successive hematopoietic cell clones support hematopoiesis. When authors compared the clonal composition of HSCs, intermediate progenitors, and mature cells in each mouse, less than 5% of HSC clones were present in mature cell populations, while the main participants in the production of mature cells were intermediate multipotent (MPP) and myeloid (MyP) precursors Based on these two experiments, the authors concluded that cells that provide stable hematopoiesis under normal conditions are incapable of transplantation and are not found in the total HSC pool. * chromatin domains associated with both repressing and activating epigenetic regulators
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