Single cell level characterization of injury-induced immune changes in MRL/MpJ knee joints
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PROVIDER: PRJNA909167 | ENA |
REPOSITORIES: ENA
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Project description:Post traumatic osteoarthritis (PTOA) is a painful joint disease characterized by the degradation of bone, cartilage, and connective tissues. PTOA is initiated by trauma to joint-stabilizing tissues, such as the anterior cruciate ligament, medial meniscus or by intra-articular fractures. In humans, ~50% of joint injuries progress to chronic PTOA, while the rest spontaneously resolve. To understand molecular programs contributing to PTOA development, we examined injury-induced fluctuations in immune cell populations and transcriptional shifts by single-cell sequencing of synovial joints in PTOA -susceptible C57BL6/J (B6) and -resistant MRL/MpJ (MRL) mice. A potent myeloid driven anti-inflammatory response was discovered in MRL injured joints that significantly contrasted the pro-inflammatory signaling seen in B6 joints. We found Trem2+ macrophages classically described as M2 (CD206+Trem2+) to be enriched in the uninjured joints of MRL mice, and these populations were consistently elevated in this strain, post injury. To evaluate whether Trem2 is essential to macrophage-mediated homeostasis in the joint, we examined Trem2 deficient mice and determined that these mice develop spontaneous OA. Overall, these data suggest that the PTOA resistant MRL mouse strain displays enhanced capacity of clearing debris and apoptotic cells induced by inflammation after injury due to an increase in activated macrophages within the synovial tissue and joint space. Furthermore, we showed that Trem2 is essential for preserving cartilage homeostasis in B6, and we postulate that the elevated levels of Trem2+ joint-resident macrophages in MRL are in part responsible for the PTOA-resistant phenotype in this strain.
2024-12-31 | GSE220167 | GEO
Project description:Injuries to the anterior cruciate ligament (ACL) often result in post-traumatic osteoarthritis (PTOA). PTOA accounts for ~12% of all osteoarthritis (OA) cases, yet the mechanisms contributing to OA after joint injury are not well understood. To better understand the molecular mechanisms behind PTOA development following ACL injury, we profiled ACL injury-induced gene expression changes in knee joints of three mouse strains with varying susceptibility to PTOA: STR/ort (highly susceptible), C57BL/6 (moderately susceptible) and super-healer MRL/MpJ (not susceptible) and identified genes differentially expressed between these strains at 0-day [before injury], 1-day, 1-week, and 2-weeks post-injury. This study highlights many new potential therapeutic targets and OA biomarkers.
2018-11-28 | GSE112641 | GEO
Project description:Comparative Transcriptomics of STR/ort, C57BL/6 and MRL/MpJ Knee Joints
| PRJNA448594 | ENA
Project description:Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+.
2008-11-01 | GSE12950 | GEO
Project description:Cryptorchidism and scrotal heating result in abnormal spermatogenesis but the mechanism(s) proscribing this temperature sensitivity are unknown. It was previously reported that the AKR/N or MRL/MpJ-+/+ mouse testis is more heat resistant than the testis from the C57BL/6 strain. We have attempted to probe into the mechanism(s) involved in heat sensitivity by examining global gene expression profiles of normal and heat-treated testes from C57BL/6, AKR/N and MRL/MpJ-+/+ mice by microarray analysis. In the normal C57BL/6 testis, 415 and 416 transcripts were differentially expressed (at least two-fold higher or lower) when compared to the normal AKR/N and MRL/MpJ-+/+ testis, respectively. The AKR/N and MRL/MpJ-+/+ strains revealed 268 differentially expressed transcripts between them. There were 231 transcripts differentially expressed between C57BL/6 and two purported heat-resistant strains, AKR/N and MRL/MpJ-+/+. Experiment Overall Design: Total RNA of testes from 3 different strains of mice, C57BL/6, AKR/N and MRL/MpJ-+/+, were analyzed using microarray 430.20 chip. All mice were 8 weeks old, 2 mice/strain.
2008-11-15 | E-GEOD-12950 | biostudies-arrayexpress
Project description:Epigenetic regulation plays essential role in cell differentiation and dedifferentiation, which are the intrinsic processes involved in regeneration. In order to investigate the epigenetic basis of regeneration capacity, we choose DNA methylation as one of the most important epigenetic mechanisms and the MRL/MpJ mouse as a model of mammalian regeneration reported to exhibit enhanced regeneration response in different organs. We report the comparative analysis of genomic DNA methylation profiles of the MRL/MpJ and the control C57BL/6J mouse. Methylated DNA immunoprecipitation (MeDIP) followed by microarray analysis using Nimblegen “3x720K CpG Island Plus RefSeq Promoter” platform were applied in order to carry out genome-wide DNA methylation profiling covering 20,404 promoter regions. We identified hundreds of hypo- and hypermethylated genes and CpG islands in heart, liver and spleen, and 37 of them in the three tissues. Decreased inter-tissue diversification and the shift of DNA methylation balance upstream the genes distinguish the genomic methylation patterns of the MRL/MpJ mouse from the C57BL/6J. Homeobox genes and a number of other genes involved in embryonic morphogenesis are significantly over-represented among the genes hypomethylated in the MRL/MpJ mouse. These findings indicate that epigenetic patterning might be a likely molecular basis of regeneration capability in the MRL/MpJ mouse.
2013-08-20 | GSE49221 | GEO
Project description:Epigenetic regulation plays essential role in cell differentiation and dedifferentiation, which are the intrinsic processes involved in regeneration. In order to investigate the epigenetic basis of regeneration capacity, we choose DNA methylation as one of the most important epigenetic mechanisms and the MRL/MpJ mouse as a model of mammalian regeneration reported to exhibit enhanced regeneration response in different organs. We report the comparative analysis of genomic DNA methylation profiles of the MRL/MpJ and the control C57BL/6J mouse. Methylated DNA immunoprecipitation (MeDIP) followed by microarray analysis using Nimblegen M-bM-^@M-^\3x720K CpG Island Plus RefSeq PromoterM-bM-^@M-^] platform were applied in order to carry out genome-wide DNA methylation profiling covering 20,404 promoter regions. We identified hundreds of hypo- and hypermethylated genes and CpG islands in heart, liver and spleen, and 37 of them in the three tissues. Decreased inter-tissue diversification and the shift of DNA methylation balance upstream the genes distinguish the genomic methylation patterns of the MRL/MpJ mouse from the C57BL/6J. Homeobox genes and a number of other genes involved in embryonic morphogenesis are significantly over-represented among the genes hypomethylated in the MRL/MpJ mouse. These findings indicate that epigenetic patterning might be a likely molecular basis of regeneration capability in the MRL/MpJ mouse. genome-wide DNA methylation profiling in the heart, liver, and spleen tissues of MRL/MpJ and C57BL/6J mouse
2013-08-20 | E-GEOD-49221 | biostudies-arrayexpress
Project description:Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Microglia control synaptic pruning during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that microglia-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased depression- and anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. To elucidate the mechanism of synaptic pruning by microglia, we sequenced the gene expression in sorted microglia from both lupus (MRL/lpr) mice and the wild-type (MRL/mpj) controls.
2024-03-27 | GSE201282 | GEO
Project description:The MRL/MpJ mouse strain is known as a model of mammalian regeneration. The strain exhibits an unusual capacity in regenerative wound healing manifested by scarless ear-hole closure and enhanced regeneration response reported in other organs. A significant feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers. As the regenerative response after injury is rather limited in mammals the MRL/MpJ mouse is a great model to study the molecular and cellular basis of scarless wound healing. We report here the analysis of genome-wide transcriptomic profiles in the heart, ear, spleen, liver and bone marrow of the MRL/MpJ mouse. We used gene expression microarray, which interrogates 44.170 of mouse transcripts, in order to identify the genes exhibiting remarkable differences in expression in the MRL/MpJ mouse compared to two reference strains: C57BL/6J and BALB/c. The comparison revealed hundreds of differentially expressed transcripts. Significant enrichments of genes engaged in retinol metabolism, peroxisome proliferator-activated receptor (PPAR), wound healing, and homeobox pathways distinguishes the differentially expressed transcripts up-regulated in the MRL/MpJ mouse, whereas the genes related to immune response, including including response to wounding are greatly enriched among those down-regulated. The same functional categories were associated with remarkable parallels between the transcriptomic patterns in murine neonates and the adult MRL/MpJ mouse.
2015-12-30 | GSE64624 | GEO
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.
2016-07-03 | E-GEOD-68038 | biostudies-arrayexpress