Cell intrinsic alterations underlie hematopoietic stem cell aging
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1132277
- author
- Rossi, Derrick J ; Bryder, David LU ; Zahn, Jacob M ; Ahlenius, Henrik LU ; Sonu, Rebecca ; Wagers, Amy J and Weissman, Irving L
- organization
- publishing date
- 2005
- 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 Academy of 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
- 2016-04-01 11:46:27
- date last changed
- 2022-04-28 19:49:59
@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}},
keywords = {{microarray; ontogeny; lineage potential; leukemia}},
language = {{eng}},
number = {{26}},
pages = {{9194--9199}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.0503280102}},
volume = {{102}},
year = {{2005}},
}