Project description:Analysis of function of CD11c+ cells from middle-aged and young mice at gene level. This experiment provided insight into the different genes that plays roles in inflammation, immune response and mainly arachidonic acid cascade that are differentiall expressed in CD11c+ cells from middle aged and young mice. Total RNA was isolated from pulmonary CD11c cells (separated using magnetic beads) from middle-aged and young mice
Project description:Analysis of function of CD11c+ cells from middle-aged and young mice at gene level. This experiment provided insight into the different genes that plays roles in inflammation, immune response and mainly arachidonic acid cascade that are differentiall expressed in CD11c+ cells from middle aged and young mice.
Project description:Recent studies show that acute injury to non-aged podocytes induces many similarities to healthy aged podocytes, such as decreased lifespan and health-span. Like healthy aged podocytes, injury to young mouse and human podocytes can induce a senescent phenotype. This begs the question if injury to young podocytes phenocopies a healthy middle-aged podocyte, and if the pathways underlying senescence and other injury responses overlap between injured young podocytes and healthy middle-aged podocytes. To address this knowledge gap we induced hypertension, a major cause of chronic kidney disease, in young mice (4m of age~20-year-old human) and in middle-aged mice (18m of age, ~55+ year old human) with deoxycorticosterone and high salt (DOCA) and compared outcomes to non-hypertensive healthy middle-aged mice. In both healthy middle-aged mice and in young mice with hypertension, the increase in age-related senescent genes p16 and p19, along with the stress-related senescent genes p21 and p53 were similar. Bulk RNA-sequencing of podocytes showed that the senescent associated secretory phenotype and individual genes from several aging gene sets were also similar between middle-aged mice and young mice with hypertension. Of the highest enriched Hallmark pathways in middle-aged podocytes, 95% were also enriched in young mice treated with DOCA. Gene set enrichment analysis of podocytes showed that 36 genes overlapped between middle-aged mice, and young and middle-aged mice given DOCA, while 119 genes identified were “DOCA-specific”. These results suggest that hypertension in young mice induces podocyte injury and an aging/senescent phenotype that is similar to the one of podocytes from healthy middle-aged mice.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:Aged hematopoietic stem cells (HSCs) display myeloid-biased differentiation and reduced regenerative potential. In this study, we uncover that P-selectin (Selp) marks a subset of aged HSCs with reduced repopulation capacity. This population of HSCs expresses a prominent aging transcriptome. Overexpression of Selp in young HSCs impaired long-term reconstitution potential and repressed erythropoiesis. We show that IL-1β is elevated in aged bone marrow and administration of IL-1β induces expression of Selp and other aging-associated genes in HSCs. Finally, we demonstrate that transplantation of aged HSCs into young recipients restores a young-like transcriptome, specifically by repressing pro-inflammatory pathways, highlighting the important role of the bone marrow microenvironment in HSC aging.