Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatial transcriptomic analysis of a pre-clinical NF1 pseudarthrosis fracture model

ABSTRACT: Spatial transcriptomic analysis of a pre-clinical NF1 pseudarthrosis fracture model

PROVIDER: PRJNA901981 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR22302417_1.fastq.gz	Fastqsanger.gz
	SRR22302417_2.fastq.gz	Fastqsanger.gz
	SRR22302418_1.fastq.gz	Fastqsanger.gz
	SRR22302418_2.fastq.gz	Fastqsanger.gz

Items per page:

1 - 4 of 4

Similar Datasets

Spatial transcriptomic analysis of a pre-clinical NF1 pseudarthrosis fracture model

Project description:Patients with Neurofibromatosis Type 1 (NF1) present with fracture pseudarthroses, though the exact mechanism underlying this abnormal healing remains unknown. Here, we performed spatial transcriptomics to spatially-define the molecular signatures across endochondral healing following fracture. Integrating single-cell sequencing of patient fracture-derived primary cells, our results provide a dynamic cellular context to the molecular dysregulation associated with somatic fracture healing defects in NF1.

2024-07-12 | GSE218046 | GEO

Molecular dissection of somatic NF1 pseudarthrosis

Project description:Neurofibromatosis Type 1 (NF1) is a tumor predisposition syndrome with pleiotropic somatic manifestations, including formation of bone pseudarthrosis after fracture. The pathogenesis of NF1 pseudarthroses remains unclear, though defects in osteogenesis have been posited. Here, we applied time-series single-cell RNA-sequencing (scRNAseq) to patient-matched control and pseudarthrosis-derived primary bone mesenchymal stromal cells (MSCs). We show that osteogenesis occurs in NF1-/- MSCs. In contrast, expression of genetic pathways associated with skeletal mineralization were reduced in NF1-/- cells compared to co-cultured NF1+/- fracture-derived cells.

2022-12-13 | GSE196652 | GEO

Single nuclei RNAseq of the bone fracture callus of Prss56-Nf1 KO mice

Project description:Periosteum deficiency affects bone regeneration, especially in the case of the bone disorder congenital pseudarthrosis of the tibia (CPT). We investigated a new mouse model of CPT caused by Nf1 inactivation in boundary cap-derivatives, the Prss56Cre; R26tdTom; Nf1fl/fl model. To investigate altered healing in this CPT model, we generated a dataset of the injured periosteum and fracture callus at day-7 post fracture from Prss56Cre; R26tdTom; Nf1fl/fl mice.

2024-07-24 | GSE232517 | GEO

Single nuclei RNAseq of the human periosteum from patients with congenital pseudarthrosis of the tibia

Project description:Congenital pseudarthrosis of the tibia (CPT) is a severe pediatric disorder affecting children. CPT is characterized by tibial bowing at birth leading to spontaneous fracture and fibrous non-union. Our study showed the presence of biallelic inactivation of the NF1 gene in the periosteum at the pseudarthrosis site. To understand the impact of NF1 mutation on the periosteum, we performed single nuclei RNAseq of pathological periosteum collected from the pseudarthrosis site and of non-pathological periosteum collected from the iliac crest of 3 CPT patients.

2024-07-24 | GSE232516 | GEO

RNAseq of periosteal stem/progenitor cells from patients with congenital pseudarthrosis of the tibia

2024-07-24 | GSE234071 | GEO

Molecular dissection of somatic NF1 pseudarthrosis

Project description:Molecular dissection of somatic NF1 pseudarthrosis

| PRJNA806667 | ENA

Spatial transcriptomics implicates impaired BMP signaling in NF1 fracture pseudarthrosis in murine and patient tissues.

Project description:The Neurofibromatosis Type 1 (NF1) RASopathy is associated with persistent fibrotic nonunions (pseudarthrosis) in human and mouse skeletal tissue. Here, we first performed spatial transcriptomics to define the molecular signatures across normal endochondral healing following fracture in mice. Within the control fracture callus, we observed spatially restricted activation of morphogenetic pathways, such as TGF-β, WNT, and BMP. To investigate the molecular mechanisms contributing to Nf1-deficient delayed fracture healing, we performed spatial transcriptomic analysis on a Postn-cre;Nf1flox/- (Nf1Postn) fracture callus. Transcriptional analyses, subsequently confirmed through p-SMAD1/5/8 immunohistochemistry, demonstrated a lack of BMP pathway induction in Nf1Postn mice. To further inform the human disease, we performed spatial transcriptomic analysis of fracture pseudarthrosis tissue from a NF1 patient. Analyses detected increased MAPK signaling at the fibrocartilaginous-osseus junction. Similar to the Nf1Postn fracture, BMP pathway activation was absent within the pseudarthrosis tissue. Our results demonstrate the feasibility to delineate the molecular and tissue-specific heterogeneity inherent in complex regenerative processes, such as fracture healing, and to reconstruct phase transitions representing endochondral bone formation in vivo. Furthermore, our results provide in situ molecular evidence of impaired BMP signaling underlying NF1 pseudarthrosis, potentially informing the clinical relevance of off-label BMP2 as a therapeutic intervention.

| S-EPMC11343587 | biostudies-literature

Spatial Transcriptomics in Bone Mechanomics: Exploring the Mechanoregulation of Fracture Healing in the Era of Spatial Omics.

Project description:In recent decades, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically-regulated fracture healing. Each cell within a fracture site resides within different local micro-environments characterized by different levels of mechanical strain - thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics based “mechanomics” platform facilitates spatially-resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro-computed tomography, spatial transcriptomics, and micro-finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and to discover mechano-responsive targets to enhance fracture healing.

2024-10-05 | GSE263658 | GEO

Spatial transcriptomic analysis of Nf1+/- mouse brain

Project description:Spatial transcriptomic analysis of Nf1+/- mouse brain

| PRJNA1096676 | ENA

Single nuclei RNAseq of the bone fracture callus of Prss56-Nf1 KO mice

Project description:Single nuclei RNAseq of the bone fracture callus of Prss56-Nf1 KO mice

| PRJNA972647 | ENA