The mammalian hematopoietic system is remarkably efficient in meeting an organism’s vital needs, yet is highly sensitive and exquisitely regulated. Much of the organismal control over hematopoiesis comes from the regulation of hematopoietic stem cells (HSCs) by specific microenvironments called niches in bone marrow (BM), where HSCs reside. The experimental studies of the last two decades using the most sophisticated and advanced techniques have provided important data on the identity of the niche cells controlling HSCs functions and some mechanisms underlying niche-HSC interactions. In this review we discuss various aspects of organization and functioning of the HSC cell niche in bone marrow. In particular, we review the anatomy of BM niches, various cell types composing the niche, niches for more differentiated cells, metabolism of HSCs in relation to the niche, niche aging, leukemic transformation of the niche, and the current state of HSC niche modeling in vitro.

In multicellular organisms, interactions between cells and intercellular communications form the very basis of the organism’s survival, the functioning of its systems, the maintenance of homeostasis and adequate response to the environment. The accumulated experimental data point to the particular importance of intercellular communications in determining the fate of cells, as well as their differentiation and plasticity. For a long time, it was believed that the properties and behavior of cells were primarily governed by the interactions of secreted or membrane-bound ligands with corresponding receptors, as well as direct intercellular adhesion contacts. In this review, we describe various types of other, non-classical intercellular interactions and communications that have recently come into the limelight—in particular, the broad repertoire of extracellular vesicles and membrane protrusions. These communications are mediated by large macromolecular structural and functional ensembles, and we explore here the mechanisms underlying their formation and present current data that reveal their roles in multiple biological processes. The effects mediated by these new types of intercellular communications in normal and pathological states, as well as therapeutic applications, are also discussed. The in-depth study of novel intercellular interaction mechanisms is required for the establishment of effective approaches for the control and modification of cell properties both for basic research and the development of radically new therapeutic strategies.

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.

Cardiovascular diseases and cancer, the leading causes of morbidity and mortality in the elderly, share some common mechanisms, in particular inflammation, contributing to their progression and pathogenesis. However, somatic mutagenesis, a driving force in cancer development, has not been generally considered as an important factor in cardiovascular disease pathology. Recent studies demonstrated that during normal aging, somatic mutagenesis occurs in blood cells, often resulting in expansion of mutant clones that dominate hematopoiesis at advanced age. This clonal hematopoiesis is primarily associated with mutations in certain leukemia-related driver genes and, being by itself relatively benign, not only increases the risks of subsequent malignant hematopoietic transformation, but, unexpectedly, has a significant impact on progression of atherosclerosis and cardiovascular diseases. In this review, we discuss the phenomenon of clonal hematopoiesis, the most important genes involved in it, its impact on cardiovascular diseases, and relevant aspects of hematopoietic stem cell biology.

Magnetic cell sorting technology stands out because of its speed, simplicity, and ability to process large cell numbers. However, it also suffers from a number of drawbacks, in particular low discrimination power, which results in all-or-none selection outcomes limited to a bulk separation of cell populations into positive and negative fractions, as well as the modest purity of the selected cells and the inability to select subpopulations of cells with high expression of a surface marker. In the present study, we developed a simple solution to this problem and confirmed the effectiveness of this approach by multiple experiments with the magnetic selection of transduced cell populations. Murine NIH 3T3 cells were transduced with the bicistronic retroviral vector constructs co-expressing fluorescent reporter proteins EGFP (enhanced green fluorescent protein) or DsRed-Express 2 and LNGFR (low-affinity nerve growth factor receptor) as surface selection markers. The effects of the magnetic selection of transduced cells with anti-LNGFR Micro Bead (MB) doses ranging from 0.5 to 80 µL have been assessed. Low doses of MBs favored the depletion of weakly positive cells from the population, resulting in the higher expression levels of EGFP or DsRed-Express2 reporters in the selected cell fractions. Low MB doses also contributed to the increased purity of the selected population, even for samples with a low initial percentage of positive cells. At the same time, high MB doses resulted in the increased yield and a more faithful representation of the original expression profiles following selection. We further demonstrate that for populations with fairly narrow distribution of expression levels, it is possible to achieve separation into high- and low-expressing subsets using the two-stage selection scheme based on the sequential use of low and high doses of MBs. For populations with broad expression distribution, a one-stage selection with low or high doses of MBs is sufficient for a clear separation of low- and high-expressing subsets in the column-retained and flow-through fractions, respectively. This study substantially extends the potential of magnetic cell sorting, and may open new possibilities in a number of biomedical applications.