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.
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.
Project description:We carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze. Keywords: age comparison
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven M-bM-^@M-^Xhotspots,M-bM-^@M-^Y seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a M-bM-^@M-^XfertileM-bM-^@M-^Y subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.