Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion
(2010) In Proceedings of the National Academy of Sciences 107(12). p.5465-5470- Abstract
- Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different... (More)
- Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1587283
- author
- Beerman, Isabel ; Bhattacharya, Deepta ; Zandi, Sasan ; Sigvardsson, Mikael ; Weissman, Irving L. ; Bryder, David LU and Rossi, Derrick J.
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- lineage specification, HSCs, leukemia
- in
- Proceedings of the National Academy of Sciences
- volume
- 107
- issue
- 12
- pages
- 5465 - 5470
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000275898300037
- scopus:77950418688
- pmid:20304793
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.1000834107
- language
- English
- LU publication?
- yes
- id
- 08f8d54a-be9e-455a-b1d3-5385d6d13f1e (old id 1587283)
- date added to LUP
- 2016-04-01 10:01:02
- date last changed
- 2022-04-27 17:29:11
@article{08f8d54a-be9e-455a-b1d3-5385d6d13f1e,
abstract = {{Aging of the hematopoietic stem cell compartment is believed to contribute to the onset of a variety of age-dependent blood cell pathophysiologies. Mechanistic drivers of hematopoietic stem cell (HSC) aging include DNA damage accumulation and induction of tumor suppressor pathways that combine to reduce the regenerative capacity of aged HSCs. Such mechanisms do not however account for the change in lymphoid and myeloid lineage potential characteristic of HSC aging, which is believed to be central to the decline of immune competence and predisposition to myelogenous diseases in the elderly. Here we have prospectively isolated functionally distinct HSC clonal subtypes, based on cell surface phenotype, bearing intrinsically different capacities to differentiate toward lymphoid and myeloid effector cells mediated by quantitative differences in lineage priming. Finally, we present data 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.}},
author = {{Beerman, Isabel and Bhattacharya, Deepta and Zandi, Sasan and Sigvardsson, Mikael and Weissman, Irving L. and Bryder, David and Rossi, Derrick J.}},
issn = {{1091-6490}},
keywords = {{lineage specification; HSCs; leukemia}},
language = {{eng}},
number = {{12}},
pages = {{5465--5470}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion}},
url = {{http://dx.doi.org/10.1073/pnas.1000834107}},
doi = {{10.1073/pnas.1000834107}},
volume = {{107}},
year = {{2010}},
}