Hematopoietic stem cell biology has focused on stem cell purification and the definition of the regulation of purified stem cells in a hierarchical system. Work on the whole unpurified murine marrow cell population has indicated that a significant number of hematopoietic stem cells, rather than being dormant, are actively cycling, always changing phenotype and therefore resistant to purification efforts by current approaches. The bulk of cycling marrow stem cells are discarded with the standard lineage negative, stem cell marker positive separations. Therefore, the purified stem cells do not appear to be representative of the total hematopoietic stem cell population. In addition, baseline hematopoiesis does not appear to be determined by the transplantable stem cells but rather by many short-lived clones of varying differentiation potential. These systems appear to be impacted by tissue derived extracellular vesicles and a number of other variables. Thus hematopoietic stem cell biology is now at a fascinating new beginning with great promise.
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