The seminal work of Till & McCulloch on CFU-Ss in 1961 proved the remarkable conjecture of Maximov some 50 years earlier on the existence of hematopoietic stem cells (HSCs) and laid foundations for their quantitative analysis. Ever since then, in this field, leading labs have dedicated significant effort to the progressive refinement of HSC features and physical isolation of more defined HSC and progenitor cell populations. This was mainly achieved with the use of monoclonal antibodies developed against various blood cell subsets, whereas transplantation into irradiated hosts has been accepted as a gold standard for quantitative functional characterization of purified cell fractions.

These efforts resulted in the appearance of a hierarchical, pyramidal model of blood cell differentiation, which presented a clear-cut scheme of stages that HCSs follow to produce huge amounts of differentiated blood cells to meet the physiological needs of an organism. The hierarchical model provided a very rational and logical explanation of how the hematopoietic system works. Alas, nature rarely follows human reasoning, and this model has not become an exception. The recent introduction of new sophisticated techniques such as single-cell transplantation, specific cell lineage/stage marking using transgenic mouse lines, cell barcoding, next-generation sequencing, single-cell transcriptome analysis, and related bioinformatics tools demonstrated that patterns of HSC differentiation are likely more complex than previously thought. Moreover, recent studies demonstrate that hematopoiesis established in irradiated animals using transplanted cell fractions, and the physiological steady-state hematopoiesis taking place in non-treated animals, not only formally differ from each other, but represent fairly different physiological systems, in which the same cell subsets may demonstrate contrasting behaviors. Given the currently accepted notion that the behavior of HSCs is determined to a large extent by the niches in which they reside, this difference may be partly explained by the irradiation damage sustained by the niche components and, possibly, peculiarities of homing to niches of various cell subsets in different physiological states. As suggested by some recent indirect data, it cannot be taken for granted that HSCs detached from their niches and subjected to significant stress during cell sorting do not substantially change their properties. If such a change occurs, this may warrant a significant revision of the results of previous experiments with transplanted sorted cells.

The true size of the “iceberg” of the complexity of the hematopoietic system is just becoming apparent and, obviously, many more studies using the most advanced techniques are needed to obtain accurate and consistent knowledge of how the hematopoietic system work. In this Special Issue, we invite researchers to submit original research articles on HSC/progenitor cells, hematopoietic microenvironment, and hematopoiesis under different conditions, or reviews on the last developments in these fields.

Dr. Alexander V. Belyavsky
Guest Editor

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• hematopoietic stem/progenitor cells
• hematopoietic differentiation
• hematopoietic niches
• niche-HSC/progenitor cell interactions
• steady-state hematopoiesis
• reconstituted hematopoiesis
• hematopoietic stress response
• cell fate tracing