Expression data of PDGFRα- and PDGFRα+ mesenchymal stem cells isolated from mouse periosteum
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154003 | GEO | 2022/02/02
REPOSITORIES: GEO
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Project description:Periosteum is a major source of skeletal stem/progenitor cells (SSPCs) during bone repair. However, the cellular composition of the periosteum is poorly characterized. Here, we provide single-cell RNAseq data of periosteal cells isolated by explant culture at steady state and at day 3 post-tibial fracture. We found that periosteal cell populations are heterogeneous containing several sub-populations of SSPCs. Upon fracture, SSPCs are activated by leaving their mesenchymal state, and engaging into fibrogenesis prior to chondrogenesis.
2022-08-10 | GSE195940 | GEO
Project description:Fracture healing is a process that involves many cell populations. In this study we characterized gene expression in a subset of cells involved in fracture healing. αSMACreERT2 mice crossed with Ai9 reporter mice that express tdTomato fluorescent protein after Cre-mediated activation were used as an experimental model. αSMA-expressing cells were labeled by tamoxifen administration, then periosteal cells from the tibia were isolated two days later (controls), or tibial fractures were performed and periosteum/soft callus tissue was collected after 2 and 6 days. The tdTomato positive cell population was isolated by flow cytometry, and subjected to microarray analysis. Histology and cell surface marker analysis indicates that αSMACreERT2 labels a mainly mesenchymal population in the periosteum that expands after fracture, and contributes to both osteogenic and chondrogenic elements of the fracture callus. We were therefore able to examine gene expression in a defined population during the early stages of fracture healing. Total RNA was obtained from the tomato positive cells within the periosteal compartment of fractures from αSMACreERT2/Ai9 mice. Control animals were given 2 doses of tamoxifen, and periosteum was collected and labeled cells sorted (8-9 sex-matched mice per group). Fractures were performed after the second dose of tamoxifen, and tomato positive cells from periosteum/callus tissue were isolated 2 and 6 days after fracture (4-8 animals per sample pooled). 3 replicates for each sample are included.
2013-11-27 | E-GEOD-45156 | biostudies-arrayexpress
Project description:Fracture healing is a process that involves many cell populations. In this study we characterized gene expression in a subset of cells involved in fracture healing. αSMACreERT2 mice crossed with Ai9 reporter mice that express tdTomato fluorescent protein after Cre-mediated activation were used as an experimental model. αSMA-expressing cells were labeled by tamoxifen administration, then periosteal cells from the tibia were isolated two days later (controls), or tibial fractures were performed and periosteum/soft callus tissue was collected after 2 and 6 days. The tdTomato positive cell population was isolated by flow cytometry, and subjected to microarray analysis. Histology and cell surface marker analysis indicates that αSMACreERT2 labels a mainly mesenchymal population in the periosteum that expands after fracture, and contributes to both osteogenic and chondrogenic elements of the fracture callus. We were therefore able to examine gene expression in a defined population during the early stages of fracture healing.
2013-11-27 | GSE45156 | GEO
Project description:Bone regeneration relies on the activation of skeletal stem cells (SSCs) that still remain poorly characterized. Here, we show that periosteum contains SSCs with high bone regenerative potential compared to bone marrow stromal cells/skeletal stem cells (BMSCs) in mice. Although periosteal cells (PCs) and BMSCs are derived from a common embryonic mesenchymal lineage, post-natally PCs exhibit greater clonogenicity, growth and differentiation capacity than BMSCs. During bone repair, PCs can efficiently contribute to cartilage and bone, and integrate long-term after transplantation. Molecular profiling uncovers genes encoding Periostin and other extracellular matrix molecules associated with the enhanced response to injury of PCs. Periostin gene deletion impairs PC functions and fracture consolidation. Periostin-deficient periosteum cannot reconstitute a pool of PCs after injury demonstrating the presence of SSCs within periosteum and the requirement of Periostin in maintaining this pool. Overall our results highlight the importance of analyzing periosteum and PCs to understand bone phenotypes.
2018-10-18 | E-MTAB-6417 | biostudies-arrayexpress
Project description:The phases of fracture healing have been well characterized. However, the exact source and genetic profile of the skeletal progenitors that participate in bone repair is somewhat unclear. Sox9 expression in skeletal elements precedes bone and cartilage formation and a Sox9+ cell type is retained in the adult periosteum. We hypothesized that Sox9+ periosteal cells are multipotent skeletal progenitors normally participating in fracture repair. To test this hypothesis we used tamoxifen (TM)-mediated lineage tracing of Sox9+ cells in Sox9CreErt2:Td-Tomato mice. TM injection indelibly labels Sox9+ cells and all their descendants with the fluorescent reporter protein Td-Tomato. Intact mouse femora were harvested 2 weeks after TM injection and analyzed by histology and immunostaining and RNA sequencing, to evaluate the skeletal distribution and gene expression profile of Td-Tomato positive cells in the adult femur. To assess the role of these cells in fracture repair, mice underwent a closed mid-diaphyseal femoral fracture and their hind limbs were harvested at 3, 9 or 56 days post-fracture to assess the contribution of Sox9+ and Td-tomato+ cells in the fracture healing process. In the intact adult mouse femur, Td-Tomato-labelled cells were observed in articular and growth plate cartilage where Sox9 is known to be expressed, but also in the primary spongiosa, periosteum, and endosteum. RNA sequencing and subsequent analysis showed that Td-Tomato positive periosteal cells were enriched in Sox9 transcripts, and transcripts for various osteogenic and chondrocyte specific genes. In a femoral fracture model, we showed that pre-labeled Td-Tomato positive descendent cells were mobilized during the fracture repair process, expanding and migrating towards the fracture site 3 days post-fracture. Here, Td-Tomato positive cells differentiate into chondrocytes and osteoblasts in the soft and hard callus, respectively, 9 days post-fracture. By 2 months post-fracture, descendants of the original Sox9 labelled cell population were prevalent in the cortex and periosteum, and amongst the differentiated osteocyte population embedded within the cortical bone. Thus, a Sox9+ progenitor population resides in the adult periosteum. Fate tracing shows that these cells likely play a substantial role in repair of the fractured femur giving rise to chondrocytes, osteoblasts and mature cortical osteocytes. To our knowledge this is the first report of this Sox9+ cell population in the periosteum of the adult long bone. Taken together with developmental studies on skeletal formation, our data suggest that Sox9+ osteochondroprogenitors play a continuous role in skeletal formation throughout life.
2018-04-25 | GSE98587 | GEO
Project description:Comprehensive analyses of miRNAs expression were performed using miRNA microarrays during osteogenic differentiation of PDGFRa+ mesenchymal progenitors isolated from human skeletal muscle to identify miRNAs that are involved in osteogenesis of PDGFRa+ mesenchymal progenitors. PDGFRa+ mesenchymal progenitors were isolated from the gluteus medius muscles of two different patients, and then subjected to osteogenic induction. Expression of miRNAs was examined using miRNA microarrays at the time points of one week and two weeks after osteogenic induction and were compared with that of uninduced cells.
2013-08-01 | E-GEOD-39361 | biostudies-arrayexpress
Project description:Bone regeneration is a highly efficient process allowing scarless healing after injury. The periosteum, the outer layer of bones, is a critical source of skeletal stem/progenitor cells (SSPCs), as well as immune, endothelial and neural cells during bone repair. In our study, we generated a single-nuclei atlas of the murine periosteal response to bone fracture. We generated single nuclei datasets from uninjured periosteum and from injured periosteum and hematoma/fracture callus at days 5 and 7 post-injury from wild-type mice.
2024-04-01 | GSE234451 | GEO
Project description:Bone fraction healing is effective in most individuals, but can be subpar and not easily treatable in patients such as the elderly, requiring new remedies. Here we tested whether activin A promotes fracture repair, inspired by recent studies showing that the protein stimulates ectopic bone formation in other systems. Using a standard mouse tibia fracture model, we found that activin A became very abundant in the developing callus soon after fracture. Single cell RNA-seq and immunostaining showed that initially, expression of the activin A-encoding gene Inhba characterized inflammatory cells and periosteal mesenchymal lineage cells. Over time, Inhba expression became prominent in a unique, highly-proliferative progenitor cell (PPC) population that displayed a myofibroblast character and was at the center of a developmental trajectory bifurcation toward cartilage and bone cells in callus. Systemic administration of a neutralizing activin A monoclonal antibody delayed fracture healing, whereas local implantation of recombinant activin A enhanced it. Cells engaged in healing produced phosphorylated SMAD2 through which activin A normally signals intracellularly, and were also positive for aSMA, a recognized marker of myofibroblasts. In vitro gain- and loss-of-function assays showed that activin A directly stimulated chondrogenesis, osteogenesis and myofibroblast differentiation in periosteal progenitors. Our study reveals that activin A is a positive regulator of fracture repair and may represent a new therapeutic tool to enhance it. Its action involves a prominent and transient PPC population with a myofibroblastic character that would rapidly gear up to bring about repair in a timely and effective manner.
2024-01-11 | GSE192630 | GEO
Project description:Challenging skeletal repairs are frequently seen in patients experiencing systemic inflammation. Current therapies aimed at mitigating inflammation or enhancing stem cell function with osteogenic factors yield inconsistent clinical outcomes. To tackle the complexity and heterogeneity of fracture repair process, we performed single-cell RNA sequencing and revealed that progenitor cell was one of the major lineages responsive to elevated inflammation and this response adversely affected progenitor differentiation by upregulation ofRbpjkin fracture nonunion.We then validated the interplay between inflammation (via Ikk2ca) and Rbpjkspecifically in progenitors by using genetic animal models. Focusing on epigenetic regulation, we identifiedRbpjkas a direct target of Dnmt3b. Mechanistically, intrinsic inflammation decreased Dnmt3b expression in progenitor cells, consequently leading toRbpjkupregulation via hypomethylation within its promoter region. We also showed thatDnmt3bloss-of-function mice phenotypically recapitulated the fracture repair defects observed inIkk2camice, whereasDnmt3btransgenic mice alleviated fracture repair defects induced byIkk2ca. Moreover,Rbpjkablation restored fracture repair in bothIkk2camice andDnmt3bloss-of-function mice. Altogether, this work elucidates a common mechanism involving NF-kB/Dnmt3b/Rbpjkaxis within the context of inflamed bone regeneration. Building upon this novel mechanistic insight, we applied local treatment with epigenetically modified progenitor cells in RA mice and showed a functional restoration of bone regeneration under inflammatory condition through an increase in progenitor differentiation potential. These findings underscore the promise of epigenetic-based therapeutic interventions for addressing delayed fracture union and nonunion particularly associated with systemic inflammation.
2024-10-22 | GSE242836 | GEO
Project description:Leptin receptor (LepR)-positive cells are key components of the bone marrow hematopoietic microenvironment, and highly enrich skeletal stem and progenitor cells that maintain homeostasis of the adult skeleton. However, the heterogeneity and lineage hierarchy within this population has been elusive. Using genetic lineage tracing and single-cell RNA sequencing, we found that Lepr-Cre labels most bone marrow stromal cells and osteogenic lineage cells in adult long bones. Integrated analysis of Lepr-Cre-traced cells under homeostatic and stress conditions revealed dynamic changes of the adipogenic, osteogenic, and periosteal lineages. Importantly, we discovered a Notch3+ bone marrow sub-population that is slow-cycling and closely associated with the vasculatures, as well as key transcriptional networks promoting osteo-chondrogenic differentiation. We also identified a Sca-1+ periosteal sub-population with high clonogenic activity but limited osteo-chondrogenic potential. Together, we mapped the transcriptomic landscape of adult LepR+ stem and progenitor cells and uncovered cellular and molecular mechanisms underlying their maintenance and lineage specification.
2021-11-17 | GSE138689 | GEO