Shaw Lab |
Baylor College of Medicine
Age-related defects in stem cells can limit proper tissue maintenance and hence contribute to a shortened life-span. Using highly purified hematopoietic stem cells (HSC) from mice aged 2 to 21 months, we demonstrate a deficit in function yet an increase in stem cell number with advancing age. Expression analysis of more than 14,000 genes identified 1500 that were age-induced and 1600 that were age-repressed. Genes associated with the stress response, inflammation, and protein aggregation dominated the upregulated expression profile, while the downregulated profile was marked by genes involved in the preservation of genomic integrity and chromatin remodeling. HSC from early-aging mice expressing a mutant p53 allele reveal that aging of stem cells can be uncoupled from aging at an organismal level. These studies show that HSC are not protected from aging. Instead, these broad epigenetic changes may drive both functional attenuation and other manifestations of aging, including the increased propensity for neoplastic transformation.
Hematopoietic stem cells (HSCs) are the best studied of all stem cells in adult organisms. These cells give rise to a board spectrum of cell types which continuously repopulate the blood. HSCs are present during the entire life of the orgamism, however they are known to gradually lose their regenerating potential as organisms age. In this experiment we adress the changes in gene expression profiles of purified hematopoietic stem cells during the aging process. We isolated purified HSCs from 2-, 6-, 12-, 21-month-old mice, extracted RNA, and measured their global transcriptional activity using Affymetrix MOE430a microarrays. The goal of this experiment is to characterize the transcriptional changes in HSCs which occur during the aging process. We used linear models to fit the time pattern of expression for each gene, and we subsequently used statistical criteria to identify those genes with significant up and down regulation during aging. Gene Ontology was used to examine the content of the two lists and to characterize the ordering of aging-associated changes in gene expression. We also used the physical map position of the regulated genes to explore the correlation between chromosomal position and the pattern of gene expression change during the aging process.