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.

Keywords: aging; bone marrow niche; clonal hematopoiesis; hematopoietic stem cell (HSC); mesenchymal stem cell (MSC); transcription factors.

Figure 1

Hematopoiesis in the embryo. (A) Sequential change of sites of hematopoiesis in the embryo. (B) Timing of primitive and definitive hematopoiesis. (C) Megaloblastic erythroid precursors and fetal erythropoietin levels. Adapted from [3,8,9].

Figure 2

Hierarchical models of hematopoiesis: (A) 2006 model, adapted from [60]; (B) modern model of continuous hematopoiesis, adapted from [59]. MPP—intermediate multipotent progenitors, CMP—common myeloid progenitors, CLP—common lymphoid progenitors, MEP—megakaryocyte/erytroid progenitors, GMP—granulocyte-macrophage progenitors, Er—erythrocytes, Mk—megakaryocytes, Gran—granulocytes, Mono—monocytes—macrophages, LMPP—lympho-myeloid polypotent progenitors, Ba—basophils, Eo—eosinophils, Ma—macrophages, Ly—lumphocytes, DC—dendritic cells.

Figure 3

Population structure of the mouse BM stroma compartment identified by single-cell transcriptome analysis: (A) distinct BM niche populations and their differentiation paths revealed by SPRING plot of single-cell transcriptomes, adapted from [90]; (B) cellular taxonomy of BM stroma and seventeen BM stroma cell clusters identified by t-Distributed stochastic neighbor embedding (t-SNE), adapted from [92]. Colors indicate graph-based cluster assignments.