RNA-seq of Tregs from injured mouse neonatal and adult tendon and spleen.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE173770 | GEO | 2025/03/01
REPOSITORIES: GEO
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Project description:Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/progenitor cells (TSPCs) remain unknown. Here, comparative single cell transcriptomics of early postnatal (2-week-old) and adult (20-week-old) mouse tendons revealed that adult tendons have reduced number of TSPCs, decreased gene expression in tendon and cartilage development, and a greater population of fibro-tenogenic cells. Notably, adult TSPCs and tenocytes exhibit increased expression of immune-response and oxidative-stress genes with higher EGFR but decreased IGF signaling. Adult tendon cells show increased levels of intracellular reactive oxygen species (ROS) in vivo. In contrast, antioxidant treatment of adult tendons significantly reduces intracellular ROS of TSPCs and improves tendon strength in vivo. Hence, these findings suggest that increased inflammation and ROS during tendon aging deteriorates tendon function and regeneration that can be mitigated by antioxidant treatment.
2025-03-03 | GSE290020 | GEO
Project description:Purpose: The goals of this study were to identify preferential gene expression signatures that are unique to Tregs in neonatal skin relative to peripheral Tregs Methods: Tregs from telogen skin and SDLNs were purified by cell sorting (using the Treg GFP reporter mouse line Foxp3-DTR/GFP) to generate mRNA transcription profiles. Results: Transcriptional profiling revealed a unique neonatal skin Treg signature relative to SDLN Tregs Conclusion: Our study represents the first detailed analysis of the neonatal skin Treg transcriptome.
2017-02-22 | GSE87130 | GEO
Project description:Tendons, which transmit force from muscles to bones, are highly prone to injury. Understanding the mechanisms driving tendon fate would impact efforts to improve tendon healing, yet this knowledge is limited. To find direct regulators of tendon progenitor emergence, we performed a zebrafish high-throughput chemical screen. We established Forskolin as a tenogenic inducer across vertebrates, functioning through Creb1a, which is required and sufficient for tendon fate. Putative enhancers containing cAMP response elements (CRE) in human, mouse and fish, drove specific expression in zebrafish cranial and fin tendons. Analysis of these genomic regions identified motifs for Ebf/EBF transcription factors. Mutation of CRE or Ebf/EBF motifs significantly disrupted enhancer activity and specificity in tendons. Zebrafish ebf1a/ebf3a mutants displayed defects in tendon formation. Notably, Creb1a/CREB1 and Ebf1a/Ebf3a/EBF1 overexpression facilitated tenogenic induction in zebrafish and human pluripotent stem cells. Together, our work reveals functional conservation of two novel transcription factors in promoting tendon fate.
2024-06-13 | GSE252165 | GEO
Project description:Tendons play a critical role in the transmission of forces between muscles and bones, and chronic tendon injuries and diseases are among the leading causes of musculoskeletal disability. For many types of tendinopathies, women have worse clinical outcomes than men. It is possible that sex-based differences in tendon morphology, composition and mechanical properties may explain the greater susceptibility of women to develop tendinopathies. Our objective was to evaluate the mechanical properties, biochemical composition, transcriptome, and cellular activity of plantarflexor tendons from four month old male and female C57Bl/6 mice using in vitro biomechanics, mass spectrometry-based proteomics, genome-wide expression profiling, and cell culture techniques. Differences between groups were tested using t-tests (α=0.05). While the Achilles tendons of male mice were approximately 6% larger than female mice (P<0.05), the cell density of female mice was around 19% larger than males (P<0.05). No significant differences in the length (P=0.34), peak force (P=0.86), peak stress (P=0.52) or energy loss during stretch (P=0.94) of plantaris tendons were observed. Mass spectrometry proteomics analysis revealed no significant difference between sexes in the abundance of major extracellular matrix (ECM) proteins like collagen types I (P=0.30) and III (P=0.68), but female mice had approximately two-fold elevations (P<0.05) in different minor ECM proteins such as fibronectin, periostin, and tenascin. Using microarray analysis, there was no significant differences (P>0.05) in the expression of most major and minor ECM genes, and in the expression of genes involved in tendon fibroblast specification or proliferation. Whole tendon qPCR analysis showed significant expression differences in elastin, scleraxis, and tenomodulin. Cell culture techniques to test the effects of sex-specific extracellular environment on cellular activity show significant differences in gene expression of type I and III collagen, Ki67, scleraxis, and tenomodulin. Histologic analysis demonstrated that males have larger tendon cross-sectional area and lower cell density when compared to females. However, there were no differences between the sexes in the mechanical properties of tendons or in the majority of primary structural extracellular matrix proteins, although elevations were observed in some minor ECM proteins. Microarray analysis also showed no significant sex-based differences in the expression of major genes associated with collagen composition, extracellular components and turnover, and fibroblast proliferation. Cell culture tests of non-autonomous cellular activity show no major signals for ECM synthesis nor fibroblast proliferation. Our results indicate that while male mice expectedly had larger tendons, male and female mice have very similar mechanical properties and biochemical composition, with small increases in minor ECM proteins and proteoglycans in female tendons. The role that these minor ECM proteins and proteoglycans play in tendon repair should be evaluated in future studies. No treatment administered, study done to evaluate normal expression profiles of male and female tenocytes. This analysis is based on a Mouse Gene ST 2.1 strip that was processed in the microarray facility in May 2015 using the wt-pico kit.
2016-08-11 | E-GEOD-85415 | biostudies-arrayexpress
Project description:Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC- senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore self-renewal and proliferation capacities, and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescues endogenous tendon regeneration and repair capacity in aged rats to levels similar to normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and downregulating mTOR signaling with induction of autophagy. Together, the strategy by pharmacological intervention with deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons. We performed mRNA microarray analyses of DMSO-treated and POG-treated Passage 12 TSPCs and identified meaningful genes in down-regulated and up-regulated group
2023-11-02 | GSE241201 | GEO
Project description:Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC- senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore self-renewal and proliferation capacities, and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescues endogenous tendon regeneration and repair capacity in aged rats to levels similar to normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and downregulating mTOR signaling with induction of autophagy. Together, the strategy by pharmacological intervention with deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons. We performed mRNA microarray analyses of DMSO-treated and POG-treated TSPCs from 18-month-old rats and identified meaningful genes in down-regulated and up-regulated group
2023-11-02 | GSE241202 | GEO
Project description:Little is understood about the roles of tendon cells during flexor tendon healing. To better understand tendon cell functions, the Scx-Cre mouse was crossed to the DTR mouse model to facilitate scleraxis lineage cell depletion prior to acute flexor tendon injury and repair. WT (cre-) and experimental (cre+) mice underwent complete transection and repair of the flexor digitorum longus tendon. Repaired tendons were harvested at 14 and 28 days post-repair for bulk RNA-Seq analysis to examine possible mechanisms driving differential healing due to Scx lineage cell depletion.
2021-02-08 | GSE156157 | GEO
Project description:We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this together with augmented HO resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.
2021-11-08 | GSE179454 | GEO
Project description:RNA-seq of Tregs from injured mouse neonatal and adult tendon and spleen.
| PRJNA726990 | ENA
Project description:Tendons are crucial connective tissues that link muscle to bone. We have demonstrated that the transcription factor Mkx plays a pivotal role in tendon development and homeostasis by regulating collagen fibril organization through tendon cell fate determination from progenitor cells and promoting the expression of type I collagen and proteoglycans. However, the precise role of Mkx in tendon homeostasis after birth is not well understood. Therefore, we generated conditional Mkx knockout mice by crossing Mkx-CreER mice with Mkx floxed mice. Following tamoxifen administration, we performed transcriptome analysis of tendons from control mice (Mkx-CreER/+ and Mkx flox/+) and Mkx conditional knockout mice (Mkx-CreER/flox)
2024-12-31 | GSE283457 | GEO