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Review
. 2015 Jan;33(1):15-20.
doi: 10.1002/stem.1829.

Concise reviews: A stem cell apostasy: a tale of four H words

Peter J Quesenberry  1 , Laura R Goldberg, Mark S Dooner
Affiliations
Review

Concise reviews: A stem cell apostasy: a tale of four H words

Peter J Quesenberry et al. Stem Cells. 2015 Jan.

Abstract

The field of hematopoietic stem cell (HSC) biology has become increasingly dominated by the pursuit and study of highly purified populations of HSCs. Such HSCs are typically isolated based on their cell surface marker expression patterns and ultimately defined by their multipotency and capacity for self-generation. However, even with progressively more stringent stem cell separation techniques, the resultant HSC population remains heterogeneous with respect to both self-renewal and differentiation capacity. Critical studies on unseparated whole bone marrow have definitively shown that long-term engraftable HSCs are in active cell cycle and thus continually changing phenotype. Therefore, they cannot be purified by current approaches dependent on stable surface epitope expression because the surface markers are continually changing as well. These critical cycling cells are discarded with current stem cell purifications. Despite this, research defining such characteristics as self-renewal capacity, lineage-commitment, bone marrow niches, and proliferative state of HSCs continues to focus predominantly on this small subpopulation of purified marrow cells. This review discusses the research leading to the hierarchical model of hematopoiesis and questions the dogmas pertaining to HSC quiescence and purification.

Keywords: Colony-forming units; Extracellular vesicles; Hematopoietic progenitor cells; Hematopoietic stem cells; Microenvironment; Tissue stem cells.

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Figures

Figure 1
Figure 1
Traditional stem cell hierarchy. In this model, pluripotent stem cells with both self-renewal and differentiative properties, give rise to increasingly lineage-restricted progenitors in a hierarchical fashion. LT-HSC = long-term hematopoietic stem cell, ST-HSC = short-term hematopoietic stem cell, MPP= multipotent progenitor cell, CLP = common lymphoid progenitor, CMP =common myeloid progenitor, Pro-B = pro B cell progenitor, Pro-T = pro T cell progenitor, GMP= granulocyte- macrophage progenitor, MEP = megakaryocyte-erythroid progenitor.
Figure 2
Figure 2
Stem cell potential within un-separated marrow is lost with stem cell purification. The multi-colored circles represent the total population of marrow cells. The non-stem cells are in blue, the conventional, highly purified stem cells are represented in red, while all other colors represent marrow cells with stem cell potential. Isolation of the small subset of highly purified quiescent stem cells leads to under-representation of the total stem cell potential within marrow.
Figure 3
Figure 3
A Stem Cell Continuum. This model shows the continuous fluctuation of progenitor/ stem cell phenotype with passage through cell cycle. LT-HSC = long-term hematopoietic stem cell.
See this image and copyright information in PMC

References

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