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PMID: 15967997 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cell intrinsic alterations underlie hematopoietic stem cell aging.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 26 ·2005-06-28 ·Pages 9194-9

Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, Weissman IL

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.

MeSH Terms
Animals Cell Lineage Cell Separation Cell Transformation, Neoplastic Cell Transplantation Cellular Senescence Down-Regulation Flow Cytometry Gene Expression Regulation Genome Hematopoiesis Hematopoietic Stem Cells/cytology Leukemia/metabolism Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Software Stem Cells/cytology,metabolism Up-Regulation
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Rossi Derrick J
Department of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. drossi@stanford.edu
Bryder David
Zahn Jacob M
Ahlenius Henrik
Sonu Rebecca
Wagers Amy J
Weissman Irving L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0503280102
Email
drossi@stanford.edu
Published
2005-06-28
Epub
2005-00-20
Pages
9194-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1153718
Subset
IM
Grants
NCI NIH HHS · R01 CA086065 · United States
NCI NIH HHS · 5 R01 CA86065 · United States
External Links
PubMed source DOI: 10.1073/pnas.0503280102 PMC Full Text View journal details
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