Project description:Recent advances have taken advantage of various animal models in HSC aging research, including certain gene mutations, chemicals, and ionizing radiation (IR). To identify the underlying mechanisms and phenotype switching in HSC aging, we employed IR-induced premature HSC aging model and performed RNA-seq of HSCs from the bone marrow (BM) of mice at three months post IR and their age-matched control mice (Ctrl).
Project description:The goal of this study is to do a global transcriptiome profiling by NGS (RNA-seq) of RNA from long bone (Femur) of young (2 months) and aged (22 months) mice to understand how the bone function and their regulations are different between these two groups. Since loss of bone is prevalent with aging, we tried to find out what all genes related to bone function are affected at the expression level with aging. Using this gene expression data, we further tried to establish a relation between the pathways and regulators that contribute to this loss of function with biological replicates.
Project description:Bone marrow (BM) is normally maintained in an immune-privileged and anti-inflammatory state, kept in check principally by regulatory T cells (Tregs). Thus, it is reasonable to expect that Tregs will help shield hematopoietic stem cells (HSCs) from excessive inflammation and thereby counteract HSC aging. Understanding how BM Tregs are adapted to the aged BM and whether they are endowed with unique functions to modulate HSC aging will identify targets for prevention of HSC aging. To identify the phenotype switching and function variation in BM Tregs with physiological and premature aging, we performed RNA-seq of Tregs from the bone marrow of mice at three months post irradiation (IR) and their age-matched control mice (Ctrl).
Project description:Aging is a universal biological phenomenon linked to many diseases, such as cancer or neurodegeneration. However, the molecular mechanisms underlying aging, or how lifestyle interventions such as cognitive stimulation can ameliorate this process, are yet to be clarified. Here, we performed a multi-omic profiling, including RNA-seq, ATAC-seq, ChIP-seq, EM-seq, SWATH-MS and single cell Multiome scRNA and scATAC-seq, in the dorsal hippocampus of young and old mouse subjects which were subject to cognitive stimulation using the paradigm of environmental enrichment. In this study we were able to describe the epigenomic landscape of aging and cognitive stimulation.
Project description:Aging is associated with osteoporosis and remodeling of bone marrow microenvironment, skewing hematopoiesis. Obesity may accelerate aging process. We use bulk-RNA sequencing to measure the transcriptomic changes of bone cells caused by long-term HFD feeding in aged mice, which mainly includes osteocytes and other bone marrow stromal cells.
2023-11-15 | GSE218105 | GEO
Project description:Aging in bone mesenchymal cells in mice
Project description:<p>Bone homeostasis mainly depends on the equilibrium of osteoclasts and osteoblasts, overactivated osteoclasts play a pivotal role in the progression of osteoporosis. Here, we revealed that Pla2g7 (phospholipase A2 group VII) was positively correlated with bone resorption in clinic. By single-cell RNA-seq data analysis, Pla2g7 was found highly enriched in osteoclasts along the developmental trajectory, which promoted osteoclast differentiation. Inhibition of Pla2g7 by Darapladib impaired both human and mice osteoclast differentiation, meanwhile, Pla2g7-deficient mice showed higher bone mass and restored the ovariectomy-induced bone loss. Mechanistically, we identified that Alox12 (arachidonate 12-lipoxygenase) mediated-arachidonic acid metabolism is a key determinant in Pla2g7 enhanced osteoclast differentiation. Its metabolite 12-HETE (12-hydroxyeicosatetraenoic acid) activated Gpr31 to regulate osteoclast formation via p38 MAPK pathway and mitochondrial energy metabolism. Collectively, our study uncovers an Alox12/12-HETE/Gpr31 axis that regulates Pla2g7-induced osteoclast differentiation, and provides a new insight for osteoporosis treatment.</p>
Project description:Using oligomycin A-treated MLO-Y4 cells and primary murine aging osteocytes as a model of cells with mitochondrial dysfunction, it is demonstrated that when mitochondria are damaged, osteocytes tend to release signaling compounds including adenosine diphosphate. We identified that the nucleotide membrane receptors P2Y2 and P2Y6 transduced the ADP signal to Mfn2, a critical regulator of osteocyte mitochondrial transfer. Whole RNA sequencing (RNA-seq) analysis of mouse cortical bone showed that mitochondrial metabolism is impaired in aged osteocytes, and there are more extracellular nucleotides released into the matrix in cortical bone in aged mice as compared to that in young mice. Aging decreases expression levels of P2Y2/P2Y6 and Mfn2.
Project description:Bone aging contributes to osteoporosis and impaired bone formation, mechanisms intricately linked to alterations in mesenchymal stem cells (MSCs) that include a metabolic decline whose precise mechanisms remain elusive. In this study, P2rx7 was identified as a key regulator of mitochondrial fitness in bone marrow MSCs during the bone aging process. To validate the role of P2rx7 in bone metabolism and aging, we deleted P2rx7 by using P2rx7 knockout mice and the mice demonstrated premature and exacerbated bone aging. What we want to explore is how P2rx7 knockout affects the genome changes of bone cells.
Project description:mDia1-miR146a double knockout (DKO) mice develop aging related MDS and eventually progress to AML at moribund stage. To investigate the rescue effect from IL6 deficiency, we created mDia1-miR146a-IL6 triple knockout (TKO) mice. Singel cell RNA seq was used to investigate the bone marrow cellularity change and pathway involved during the disease progression.