Cell Stem Cell
Volume 22, Issue 4, 5 April 2018, Pages 600-607.e4
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Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment

https://doi.org/10.1016/j.stem.2018.03.013Get rights and content
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Highlights

  • Single-cell transplantation reveals dramatic age-related changes in HSC composition

  • MyRPs/MySCs increase with age as a frequency of whole BM cells and the HSC compartment

  • Latent-HSCs were identified exclusively in the aged bone marrow

  • Latent-HSCs have restricted potential in primary, but not secondary, transplants

Summary

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.

Keywords

hematopoietic stem cell
hematopoiesis
HSC
aging
stem cell aging
single cell
clonal analysis
multipotency
self-renewal

Cited by (0)

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These authors contributed equally

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Present address: Tsinghua-Peking Center for Life Sciences, Tsinghua University Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China

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