An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state.

@article{Wahlestedt2013AnEC,
  title={An epigenetic component of hematopoietic stem cell aging amenable to reprogramming into a young state.},
  author={Martin Wahlestedt and Gudmundur L. Norddahl and Gerd Sten and Amol Ugale and Mary-Ann Micha Frisk and Ragnar Mattsson and Tomas Deierborg and Mikael Sigvardsson and David Bryder},
  journal={Blood},
  year={2013},
  volume={121 21},
  pages={
          4257-64
        }
}
Aging of hematopoietic stem cells (HSCs) leads to several functional changes, including alterations affecting self-renewal and differentiation. Although it is well established that many of the age-induced changes are intrinsic to HSCs, less is known regarding the stability of this state. Here, we entertained the hypothesis that HSC aging is driven by the acquisition of permanent genetic mutations. To examine this issue at a functional level in vivo, we applied induced pluripotent stem (iPS… 

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Aging of the hematopoietic system

  • H. Snoeck
  • Biology, Medicine
    Current opinion in hematology
  • 2013
It is argued that age-related changes in HSCs and in the hematopoietic system may not entirely be due to a degenerative aging process, but are the result of developmental and stem cell-protective mechanisms aimed at maximizing fitness during reproductive life.

OPINION Aging of the hematopoietic system

It is argued that age-related changes in HSCs and in the hematopoietic system may not entirely be due to a degenerative aging process, but are the result of developmental and stem cell-protective mechanisms aimed at maximizing fitness during reproductive life.

The aging hematopoietic stem cell niche: Phenotypic and functional changes and mechanisms that contribute to hematopoietic aging.

This review provides an overview of the major phenotypes associated with hematopoietic aging and discusses recent research investigating cell-intrinsic and cell-extrinsics mechanisms of hematopolietic stem cell (HSCs) aging.

Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate

Functional and molecular evaluations reveal haematopoiesis from these iPS clones to be indistinguishable from that associating with young mice, providing direct support to the notion that several key functional attributes of HSC ageing can be reversed.
...

References

SHOWING 1-10 OF 39 REFERENCES

Cell intrinsic alterations underlie hematopoietic stem cell aging.

Estimation of cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells from young and old mice found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential.

Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion

Data is presented supporting a model in which clonal expansion of a class of intrinsically myeloid-biased HSCs with robust self-renewal potential is a central component of hematopoietic aging.

Reduced repression of cytokine signaling ameliorates age‐induced decline in hematopoietic stem cell function

It is suggested that enhanced cytokine signaling can counteract functional age‐related HSC decline and give rise to a hematopoietic system with a balanced lineage distribution.

Hematopoietic stem cell ageing is uncoupled from p16INK4A-mediated senescence

Testing multiple functional and molecular parameters indicative of p16INK4A activity in primary aged murine hematopoietic stem cells indicates that increased senescence as mediated by the p16ink4A tumor suppressor has only a minor function as an intrinsic regulator of steady-state HSC ageing in vivo.

Major Age‐Related Changes Of Mouse Hematopoietic Stem/Progenitor Cells

A stem cell basis for B‐cell immuno‐senescence and the increased incidence of myelocytic leukemia in elderly people is suggested and a complex relationship between MDR activity and HSC function during aging is suggested.

Epigenetic memory in induced pluripotent stem cells

It is observed that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates.

Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation

These studies show that hematopoietic stem cells are not protected from aging, and loss of epigenetic regulation at the chromatin level may drive both functional attenuation of cells, as well as other manifestations of aging, including the increased propensity for neoplastic transformation.

Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells

It is shown that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns, and it is demonstrated that cellular origin influences the in vitro differentiation potentials of iPSC into embryoid bodies and different hematopsic cell types.