Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly. 3 old mice and 5 young mice were assayed
Project description:Loss of Phf6 prevents the functional decline and immunophenotypic changes associated with age-related, long-term repopulating hematopoietic stem cell (LT-HSC) exhaustion. To identify the underlying molecular mechanisms that account for these differences, we performed RNA-seq profiling of LT-HSCs isolated from the bone marrow of Phf6 wild-type and knock-out, young (16-week-old) and aged (24-month-old) C57BL/6 mice. Our analysis revealed that LT-HSCs isolated from 24-month-old, Phf6 knockout mice retained the molecular signatures associated with young LT-HSCs whereas LT-HSCs isolated from aged, Phf6 wild-type mice acquired signatures consistent with HSC exhaustion. Mechanistically, these data revealed important roles for key metabolic pathways including glutathione metabolism and sterol biosynthesis, as well as cell-cell interaction and signaling pathways such as the interferon and TGF-beta responses.
Project description:Here, we use single-cell RNA-Seq to examine variation between individual hematopoietic stem and progenitor cells from two mouse strains (C57BL/6 and DBA/2) as they age. We prepared libraries from long-term (LT-HSCs) (LSK CD150+CD48-), short-term hematopoietic stem cells (ST-HSCs) (LSK CD150-CD48-) and multipotent progenitors (MPPs) (LSK CD150+CD48+) from young (2-3 months) and old mice (22 months for C57BL/6 and 20 months for DBA/2). Population controls for each cell type and age were isolated by sorting processed in parallel.
Project description:Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions. Keywords: The effect of excises in young and old human subjects by transcription profiling
Project description:In this project two sets of proteomic experiments were performed: (1) Autophagosome content profiling: Autophagosomes were isolated from cultured primary lung endothelial cells of LC3-GFP and WT mice using anti-GFP uMACS (n=3 biological replicates). (2) Expression proteomics: Protein lysates from endothelial cells of n=3 young and old WT mice, young and old vecCRE-ATG5flox mice (ATG5 KO mice).
Project description:Comprehensive analysis of gene expression in hematopoietic stem and progenitor cells from young and old mice. Gene expression profiling of young and old mouse hematopoietic stem and progenitor cells by Gene Expression Commons system.
Project description:With our experiments we have shown LP(Lactobacillus plantarum) mediated modification of immunogenic bone marrow derived dendritic cells (BMDCs) to acquire tolerogenic phenotype, to unravel the molecular mechanism of LP mediated immunomodulation we performed global transcriptomic Gut of old mice was reconstituted with LP, and RNA was extracted from LPS stimulated BMDCs from young, young treated with antibiotic cocktail, old and old-LP groups for gene array profiling by Agilent GeneChips.
Project description:Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
Project description:Muscle stem cells (MuSCs) are required for muscle regeneration. In resting muscles, MuSCs are kept in quiescence. After injury, MuSCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. Age-associated impairments in stem cell functions correlate with a decline in somatic tissue regeneration capacity during aging. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we obtained quisecent MuSCs from young, old, geriatric mice for high resolution mass spectrometry Bruker timsTOF Pro. By comparison of young proteome to old MuSCs proteome or geriatric MuSC proteome, we identified the pathways that are differentially during aging.
Project description:To investigate why dipeptides accumulate in immature CML cells, we examined upstream gene expression patterns. We isolated the most primitive long-term stem cells, short-term stem cells, and KLS- progenitor cells from healthy littermate control and CML-affected mice and performed gene expression profiling using next-generation RNA-sequencing. Gene expression profiles of the most primitive long-term (LT) stem cells (CD150+CD48-CD135-KLS+ cells), short-term (ST) stem cells (CD150-CD48-CD135- KLS+ cells), and KLS- progenitor cells from healthy littermate control and CML-affected mice