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Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (single cell RNA-Seq)

ABSTRACT: Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (single cell RNA-Seq)

PROVIDER: PRJNA416038 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6224520_1.fastq.gz	Fastqsanger.gz
	SRR6224520_2.fastq.gz	Fastqsanger.gz
	SRR6224521_1.fastq.gz	Fastqsanger.gz
	SRR6224521_2.fastq.gz	Fastqsanger.gz
	SRR6224522_1.fastq.gz	Fastqsanger.gz

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Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing

Project description:Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing

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Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (batch RNA-Seq)

Project description:Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (batch RNA-Seq)

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Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing (batch RNA-Seq)

Project description:FACS sorted 4 bulk cell population from mouse femur (P6) were subjected to RNA sequencing. The samples were periosteal stem cell (PSC), progenitor population type 1 (PP1), progenitor population 2 (PP2) and CTSK-mGFP negative mesenchymal stem cells (MSC). The aim of this project was to obtain Differentially expressed gene list for each cell types as well as compare transcriptinal profile between each population.

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Transcriptional profiling of intramembranous and endochondral ossification after fracture in mice

Project description:Bone fracture repair represents an important clinical challenge with nearly 1 million non-union fractures occurring annually in the U.S. Gene expression differs between non-union and healthy repair, suggesting there is a pattern of gene expression that is indicative of optimal repair. Despite this, the gene expression profile of fracture repair remains incompletely understood. In this work, we used RNA-seq of two well-established murine fracture models to describe gene expression of intramembranous and endochondral bone formation. We used top differentially expressed genes, enriched gene ontology terms and pathways, callus cellular phenotyping, and histology to describe and contrast these bone formation processes across time. Intramembranous repair, as modeled by ulnar stress fracture, and endochondral repair, as modeled by femur full fracture, exhibited vastly different transcriptional profiles throughout repair. Stress fracture healing had enriched differentially expressed genes associated with bone repair and osteoblasts, highlighting the strong osteogenic repair process of this model. Interestingly, the PI3K-Akt signaling pathway was one of only a few pathways uniquely enriched in stress fracture repair. Full fracture repair involved a higher level of inflammatory and immune cell related genes than did stress fracture repair. Full fracture repair also differed from stress fracture in a robust downregulation of ion channel genes following injury, the role of which in fracture repair is unclear. This study offers a broad description of gene expression in intramembranous and endochondral ossification across several time points throughout repair and suggests several potentially intriguing genes, pathways, and cells whose role in fracture repair requires further study

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Project description:Mechanosensitive Piezo1 is crucial for periosteal stem cell-mediated fracture healing

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Fracture healing in osteoporotic mice

Project description:Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice. To investigate bone healing in osteoporosis, we performed fracture healing studies in wild-type mice (C57BL/6 genetic background) and the low bone mass strains Col1a1-Krm2 and Lrp5-/- (Schulze et al., 2010; Kato et al., 2002). Osteotomy was set in femora of female mice and stabilized by a semi-rigid fixator to allow fast bone healing (RM-CM-6ntgen et al., 2010). 21 days post surgery we analyzed the fracture calli by biochemical/histological methods, as well as micro-computed tomography, and observed impaired fracture healing in Col1a1-Krm2 and Lrp5-/- mice in comparison to wild-type. To identify genes that may be responsible for the impaired healing in osteoporotic mice, we performed microarray analysis of three independent callus samples of each genotype. The callus tissue was taken 10 days after surgery, because extensive bone formation took place at this point.

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Single nuclei RNAseq of the periosteal response to bone fracture in mice

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.

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Project description:Bone fracture healing requires skeletal stem cells (SSCs), which facilitate intramembranous ossification and endochondral ossification in long bone fractures. Although the periosteum is necessary for bone homeostasis and regeneration, the in vivo origin and regulatory mechanisms of periosteal SSCs (P-SSCs) remain unclear. Here, we identified Postn+ P-SSCs at the cambium layer of the periosteum that actively orchestrate regeneration in response to bone injury. Notably, the Postn+ P-SSCs that arise during bicortical fractures are likely derived from Gli1+ P-SSCs. In addition, Postn+ cell ablation compromises cortical bone homeostasis and bone regeneration. The IGF signal is indispensable in the regulatory effect of Postn+ P-SSCs on bicortical fractures since the genetic deletion of Igf1r in Postn+ cells dampens bone fracture healing. Taken together, adult Postn+ cells are region-specific P-SSCs that contribute to bone homeostasis and regeneration and are partially dependent upon IGF signaling.

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Discovery of a periosteal stem cell mediating intramembranous bone formation and fracture healing

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

2018-08-13 | GSE106237 | GEO