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

Beerman, Isabel; Bhattacharya, Deepta; Zandi, Sasan; Sigvardsson, Mikael; Weissman, Irving L.; Bryder, David LU and Rossi, Derrick J. (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)
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author
organization
publishing date
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 Acad Sciences
external identifiers
  • wos:000275898300037
  • scopus:77950418688
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
2010-04-26 15:48:28
date last changed
2018-07-15 03:04:25
@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},
  keyword      = {lineage specification,HSCs,leukemia},
  language     = {eng},
  number       = {12},
  pages        = {5465--5470},
  publisher    = {National Acad 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},
  volume       = {107},
  year         = {2010},
}