Fgf18 marks reserve skeletal stem or progenitor cells in the outer periosteum responsible for bone fracture repair
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE285912 | GEO | 2026/05/31
REPOSITORIES: GEO
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Project description:Purpose: Periosteum is highly involved in bone generation. We used single cell RNA sequencing(scRNA-seq) to analyze the heterogenity of periosteum from db/+ and db/db mice, fractured or post-fractured, and the homology of periosteum from mice and human.
2025-07-31 | GSE281902 | GEO
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 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: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:Bone regeneration is a highly efficient process allowing scarless healing after injury. Yet, musculoskeletal traumatic injury, when fracture is combined with adjacent muscle injury, alters bone healing leading to fibrous nonunion. 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. We generated single nuclei datasets from the injured perioteum and hematoma at day 1-post fracture and from the hematoma/callus at day 5 post-musculoskeletal traumatic injury. These datasets were analyzed in combination with datasets from GSE234451.
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Project description:The development of alternatives for autologous bone grafts is a major focus of bone tissue engineering. To produce living implants, the use of skeletal stem and progenitor cells (SSPCs) are envisioned as key ingredients. SSPCs can be obtained from bone marrow, adipogenic tissue, dental pulp and periosteum. Human periosteum-derived cells (hPDCs) exhibit a number of progenitor characteristics and have well-documented in vivo bone formation capacity. Here, we have characterized and compared hPDCs derived from tibia with new sources of hPDCs, i.e. from maxilla and mandible (craniofacial hPDCs, as a potential source for tissue engineered implants for craniofacial applications.
2020-11-07 | GSE149167 | GEO
Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
2024-06-01 | GSE190483 | GEO
Project description:Skeleton system has shown high cell heterogeneousity. Different subpopulation of skeleton stem cells or mesenchymal stem cells have been identified by using varied protein markers. However, the decline of which cell types are responsible for age-related bone loss and what characteristic changes of these cells during aging remain to be determined. In the current study, we constructed a conditional premature aging model by deletion of Zmpste24 (Z24) in different cell types. We found that Prx1Cre; Z24fl/fl mice displayed bone loss while OsxCre; Z24fl/fl mice did not, indicating the populations of Prx1Cre +Osxcre- cells are responsible for age-related bone loss. Using single-cell RNA sequencing, we found two populations exit in Prx1Cre; Ai9+ mice but not in OsxCre; Ai9+ mice. Most strikingly, these two populations were declined in Prx1Cre;Z24fl/fl mice, compared to Prx1Cre;Z24fl/+ mice. The two populations, one is Prx1Cre;CD73+ resident in growth plate, called gpSSCs, responsible for trabecular bone loss. Another is Prx1Cre; Sca1+ resident in periosteum, called pSSCs, responsible cortical bone decrease. More importantly, the naturally aged mice also showed the decrease of these two cell types. By integration of chromatin and transcriptional profiling, we found that these two cell populations displayed increased p53 mediated DNA damage and decreased extracellular matrix (ECM) constituents, supporting the degeneration of two populations during aging. Finally, we found that AgrcCreER Z24fl/fl mice displayed the decrease of trabecular bone, but not cortical bone, consistent with AgrcCreER could only label trabecular bone, but not cortical bone. Overall, our study identified two skeleton stem cells, gpSSCs and pSSCs, which are responsible for the age-related bone loss in trabecular bone and cortical bone, respectively.
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Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
2024-06-01 | GSE190476 | GEO
Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
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