In human bone marrow, the HSC population is highly enriched within the Lin −CD34 +CD38 −CD90 +CD45RA − population ( 19– 24). In humans, age-associated hematopoietic changes include decreased bone marrow cellularity ( 14), declines in lymphopoiesis ( 7, 15, 16), red cell abnormalities such as anemia ( 17), and increases in the incidence of myelodysplastic syndromes, myeloproliferative disorders, and myeloid malignancies ( 18). The majority of HSC from elderly mice are myeloid biased, whereas most HSC from young mice are balanced in lymphopoiesis and myelopoiesis ( 8– 13). In the mouse, we and others have identified distinct clonal subtypes of HSC that differentially respond to external cytokine stimuli and exhibit lineage bias upon transfer to irradiated hosts ( 8– 13). Additionally, elderly mouse HSC exhibit a marked decrease in lymphopoiesis and increase in myelopoiesis ( 2, 6). We and others have found that as mice age, their HSC numbers increase, but competitive repopulation ability is reduced, suggesting a decrease in mouse HSC function with age ( 2– 7). Though the mechanisms of aging in the hematopoietic system are comprised of a combination of cell-intrinsic and -extrinsic causes that ultimately alter the generation and function of mature blood lineages, there is increasing evidence that implicates alterations within the HSC population as one of the mechanisms behind hematopoietic aging. Hematopoiesis is initiated by hematopoietic stem cells (HSC) that can self-renew and progressively differentiate into a hierarchy of committed progenitors that ultimately give rise to mature blood cells ( 1). These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. The 5-lineages experiments brought amazing discoveries, there are a dozen distinct hematopoietic cell types, and maybe hundreds of sub-types waiting for additional studies.In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. To follow one of the intriguing points of this review: are such putative microglia- or macrophage-stem-cell the origin of any separate malignancy? By this review definitions, there should be a defined stem-cell for these cells there is a basic interest and a clinical need to identify these "primitive" and restricted stem cells. Moreover, recent studies suggest bone-marrow independent branches of hematopoietic cells, such as the brain's microglia, and tissue macrophages. Probably due to the limited space, this review lacks the embryonic-origin of HSCs, which is a major interest of the field, and for any adult stem cells. Even better- they define some of the cutting-edge questions and set the course for the coming years. It is very helpful of Ryo Yamamoto, Adam Wilkinson, and Hiromitsu Nakauchi to put such a concise nomenclature and define clearly what we know. Beautiful review that greatly helps the HSC field, and stem cells research in general.Īuthors have made many of the seminal studies that changed the "classical" hematopoietic-TREE into a SHRUB (?) as presented in its schematic Figure.
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