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Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs.

Original publication

DOI

10.1016/j.stem.2018.03.013

Type

Journal article

Journal

Cell Stem Cell

Publication Date

05/04/2018

Volume

22

Pages

600 - 607.e4

Keywords

HSC, aging, clonal analysis, hematopoiesis, hematopoietic stem cell, multipotency, self-renewal, single cell, stem cell aging, Aging, Animals, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Mice