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Cell intrinsic alterations underlie hematopoietic stem cell aging

Rossi, Derrick J; Bryder, David LU ; Zahn, Jacob M; Ahlenius, Henrik LU ; Sonu, Rebecca; Wagers, Amy J and Weissman, Irving L (2005) In Proceedings of the National Academy of Sciences 102(26). p.9194-9199
Abstract
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We 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. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid... (More)
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We 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. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microarray, ontogeny, lineage potential, leukemia
in
Proceedings of the National Academy of Sciences
volume
102
issue
26
pages
9194 - 9199
publisher
National Acad Sciences
external identifiers
  • pmid:15967997
  • scopus:21544467270
ISSN
1091-6490
DOI
10.1073/pnas.0503280102
language
English
LU publication?
yes
id
39b80f5f-f86c-4f20-8eaf-f69a25808d8d (old id 1132277)
date added to LUP
2008-06-30 10:48:37
date last changed
2017-10-29 03:28:20
@article{39b80f5f-f86c-4f20-8eaf-f69a25808d8d,
  abstract     = {Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We 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. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.},
  author       = {Rossi, Derrick J and Bryder, David and Zahn, Jacob M and Ahlenius, Henrik and Sonu, Rebecca and Wagers, Amy J and Weissman, Irving L},
  issn         = {1091-6490},
  keyword      = {microarray,ontogeny,lineage potential,leukemia},
  language     = {eng},
  number       = {26},
  pages        = {9194--9199},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Cell intrinsic alterations underlie hematopoietic stem cell aging},
  url          = {http://dx.doi.org/10.1073/pnas.0503280102},
  volume       = {102},
  year         = {2005},
}