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: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:Evidence indicates that the integrity of in utero embryonic development can influence late life healthy or unhealthy aging. However, specific links between embryonic development and late life aging are not well defined. Histone chaperone HIRA is thought to play a role in both early development and aging. Here, we explore the relationship between HIRA’s roles in development and aging by comparing lineage-specific constitutive and conditional Hira knock out in the murine pigmentary system, with constitutive knock out initiated during embryogenesis and conditional knock out in young adults. Embryonic Hira knockout leads to reduced melanoblast numbers during embryogenesis but wild type numbers of differentiated melanocytes at birth, normally functioning juvenile and young adult melanocyte stem cells (McSCs), and only a very mildly hypopigmented first hair coat. However, on closer analysis of these mice, Hira knockout melanocytic cells of newborn mice exhibit molecular markers characteristic of cell aging and proliferative deficits. As they age, mice with Hira knock out initiated during embryogenesis display marked defects in McSC maintenance and premature hair graying. Importantly, these defects are only observed when HIRA is inactivated during embryogenesis, but not in young adults. This genetic model shows that HIRA function during early development lays a foundation for subsequent maintenance of adult tissue specific stem cells during aging.
Project description:Evidence indicates that the integrity of in utero embryonic development can influence late life healthy or unhealthy aging. However, specific links between embryonic development and late life aging are not well defined. Histone chaperone HIRA is thought to play a role in both early development and aging. Here, we explore the relationship between HIRA’s roles in development and aging by comparing lineage-specific constitutive and conditional Hira knock out in the murine pigmentary system, with constitutive knock out initiated during embryogenesis and conditional knock out in young adults. Embryonic Hira knockout leads to reduced melanoblast numbers during embryogenesis but wild type numbers of differentiated melanocytes at birth, normally functioning juvenile and young adult melanocyte stem cells (McSCs), and only a very mildly hypopigmented first hair coat. However, on closer analysis of these mice, Hira knockout melanocytic cells of newborn mice exhibit molecular markers characteristic of cell aging and proliferative deficits. As they age, mice with Hira knock out initiated during embryogenesis display marked defects in McSC maintenance and premature hair graying. Importantly, these defects are only observed when HIRA is inactivated during embryogenesis, but not in young adults. This genetic model shows that HIRA function during early development lays a foundation for subsequent maintenance of adult tissue specific stem cells during 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. 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.
