The slippery slope of hematopoietic stem cell aging
(2017) In Experimental Hematology 56. p.1-6- Abstract
The late stages of life, in most species including humans, are associated with a decline in the overall maintenance and health of the organism. This applies also to the hematopoietic system, where aging is not only associated with an increased predisposition for hematological malignancies, but also identified as a strong comorbidity factor for other diseases. Research during the last two decades has proposed that alterations at the level of hematopoietic stem cells (HSCs) might be a root cause for the hematological changes observed with age. However, the recent realization that not all HSCs are alike with regard to fundamental stem cell properties such as self-renewal and lineage potential has several implications for HSC aging,... (More)
The late stages of life, in most species including humans, are associated with a decline in the overall maintenance and health of the organism. This applies also to the hematopoietic system, where aging is not only associated with an increased predisposition for hematological malignancies, but also identified as a strong comorbidity factor for other diseases. Research during the last two decades has proposed that alterations at the level of hematopoietic stem cells (HSCs) might be a root cause for the hematological changes observed with age. However, the recent realization that not all HSCs are alike with regard to fundamental stem cell properties such as self-renewal and lineage potential has several implications for HSC aging, including the synchrony and the stability of the aging HSC state. To approach HSC aging from a clonal perspective, we recently took advantage of technical developments in cellular barcoding and combined this with the derivation of induced pluripotent stem cells (iPSCs). This allowed us to selectively approach HSCs functionally affected by age. The finding that such iPSCs were capable of fully regenerating multilineage hematopoiesis upon morula/blastocyst complementation provides compelling evidence that many aspects of HSC aging can be reversed, which indicates that a central mechanism underlying HSC aging is a failure to uphold the epigenomes associated with younger age. Here we discuss these findings in the context of the underlying causes that might influence HSC aging and the requirements and prospects for restoration of the aging HSC epigenome.
(Less)
- author
- Wahlestedt, Martin LU and Bryder, David LU
- organization
- publishing date
- 2017-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Experimental Hematology
- volume
- 56
- pages
- 6 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:28943295
- wos:000416614100001
- scopus:85033707702
- ISSN
- 0301-472X
- DOI
- 10.1016/j.exphem.2017.09.008
- language
- English
- LU publication?
- yes
- id
- 4e1ee5f4-280a-41aa-b234-4c0bb2a857b8
- date added to LUP
- 2017-12-12 07:33:34
- date last changed
- 2025-01-08 02:54:15
@article{4e1ee5f4-280a-41aa-b234-4c0bb2a857b8,
abstract = {{<p>The late stages of life, in most species including humans, are associated with a decline in the overall maintenance and health of the organism. This applies also to the hematopoietic system, where aging is not only associated with an increased predisposition for hematological malignancies, but also identified as a strong comorbidity factor for other diseases. Research during the last two decades has proposed that alterations at the level of hematopoietic stem cells (HSCs) might be a root cause for the hematological changes observed with age. However, the recent realization that not all HSCs are alike with regard to fundamental stem cell properties such as self-renewal and lineage potential has several implications for HSC aging, including the synchrony and the stability of the aging HSC state. To approach HSC aging from a clonal perspective, we recently took advantage of technical developments in cellular barcoding and combined this with the derivation of induced pluripotent stem cells (iPSCs). This allowed us to selectively approach HSCs functionally affected by age. The finding that such iPSCs were capable of fully regenerating multilineage hematopoiesis upon morula/blastocyst complementation provides compelling evidence that many aspects of HSC aging can be reversed, which indicates that a central mechanism underlying HSC aging is a failure to uphold the epigenomes associated with younger age. Here we discuss these findings in the context of the underlying causes that might influence HSC aging and the requirements and prospects for restoration of the aging HSC epigenome.</p>}},
author = {{Wahlestedt, Martin and Bryder, David}},
issn = {{0301-472X}},
language = {{eng}},
month = {{12}},
pages = {{1--6}},
publisher = {{Elsevier}},
series = {{Experimental Hematology}},
title = {{The slippery slope of hematopoietic stem cell aging}},
url = {{http://dx.doi.org/10.1016/j.exphem.2017.09.008}},
doi = {{10.1016/j.exphem.2017.09.008}},
volume = {{56}},
year = {{2017}},
}