Replication Stress is a Potent Driver of Functional Decline in Aging in Hematopoietic Stem Cells. Mus musculus

To understand at the molecular level the differences between old HSCs and young HSCs we have performed genome-wide analyses using Affymetrix Gene ST 1.0 microarrays with FACS purified cell populations. In contrast to other datasets comparing young and old HSCs, we compared both young and old HSCs and GMPs, and subtracted for genes that were also differentially expressed between young and old GMPs using a zero-intercept linear model. This allowed us to identify 913 significantly differentially expressed genes that were specific to old HSCs and segregated into different clusters. Overall design: Hematopoietic Stem Cells (HSC) (Lin-/cKit+/Sca1+/Flk2-/CD48-/CD150+) and Granulocyte/Macrophage progenitors (GMP) (Lin-/cKit+/Sca1-/FcyR+/CD34+) were isolated from young (6-12 weeks) and old (22-30 months) C57Bl/6 mice and subjected to microarray analysis wild type C57Bl/6 mice