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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration scRNA

ABSTRACT: Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration scRNA

PROVIDER: PRJNA787272 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17171645_1.fastq.gz	Fastqsanger.gz
	SRR17171645_2.fastq.gz	Fastqsanger.gz

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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration scRNA

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

Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration [veh vs pos]

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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration

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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration [neg vs pos]

Project description:Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration [neg vs pos]

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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration [veh vs pos]

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Discovery of neuro- and vascular-associated periosteum-resident macrophages essential for cortical bone regeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-06-01 | GSE190485 | GEO

Premature aging in growth-plate and periosteum resident skeletal stem cells is responsible for bone loss

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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Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin

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.

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Premature aging in growth-plate and periosteum resident skeletal stem cells is responsible for bone loss

Project description:Premature aging in growth-plate and periosteum resident skeletal stem cells is responsible for bone loss

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