Similar Datasets
Project description:Collagen I and fibromodulin induce tenogenic differentiation of hASCs
| PRJNA1032430 | ENA
Project description:Chronic tissue injury caused by localized radiotherapy alters the microenvironment including stem cell niches, and leads to wound healing inhibition. We precultured human adipose-derived stem cells (hASCs) on recombinant collagen peptide (RCP) scaffold, and the cells showed upregulation of cell proliferation genes and extracellular-matrix genes, compared with hASCs cultured on normal dish. Also, pathway analyses revealed hASC cultured on RCP had gene expression pattern of inflammatory suppression, cell growth promotion and activation of certain growth factors including VEGF, HGF and TGF-β1, suggesting biological activity of RCP scaffold. In chronic radiation mice models (a total of 20 Gy radiation 4 weeks in advance), treatment with hASCs and human umbilical vein endothelial cells (HUVECs) precultured on RCP achieved the best wound healing acceleration, compared with hASC on RCP group, RCP only group, and control group which showed better healing in this order. RCP scaffold, and combination use of hASCs and ECs, could be a safe, effective and practical therapeutic tool for a variety of stem cell-depleted conditions such as chronic postirradiation tissues.
2019-08-03 | GSE85129 | GEO
Project description:Single cell RNA sequencing was used to compare cells cultured using a tenogenic differentiation protocol. Cells included primary fibroblasts extracted from a tenolysis tissue specimen, mesenchymal progenitor cells (iMPCs) differentiated from induced pluripotent stem cells that were reprogrammed from the primary fibroblasts, as well as primary bone-marrow mesenchymal stromal cells (MSCs) from a different donor. For each cell type, cells were cultured for 21 days using a tenogenic differentiation protocol from STEMCELL Technologies. An undifferentiated negative control of each original cell type was cultured in parallel for 21 days along with a shorter culture of only 7 days. After culture, the gene expression profile of each sample was compared to assess tenogenic differentiation and heterogeneity in the cultures. It was found that tenogenic differentiation of iMPCs resulted in a small population of tenocyte-like cells with positive expression of tenogenic markers TNMD, SCX, and MKX. However, the cultures were heterogenous and had significant populations of non-tenocyte like cells. Furthermore, negative control samples also exhibited low expression of tendon markers in the abscence of tenogenic differentiation media. This study demonstrates that culture of mesenchymal progenitor cells for 21 days at high density alone is enough to promote some tenogenic differentiation. While addition of the tenogenic differentiation media led to more differentiation, the improvement was subtle and there is significant off-target differentiation that can be improved with alteration of the protocol.
2026-07-07 | GSE332930 | GEO
Project description: Not available
| S-EPMC10719373 | biostudies-literature
Project description:The musculoskeletal system is integrated by tendons that are characterized by expression of a functionally important transcription factor Scleraxis (Scx). To date, there has been no solid culture system for tenogenic differentiation. Here we developed the tenocyte induction method using induced pluripotent stem cells established from ScxGFP transgenic mice by monitoring fluorescence that reflects a series of dynamic differentiation process. Among several developmentally relevant factors, TGF-2 was the most potent inducer for differentiation of tenocytes expressing Tenomodulin, a mature differentiation marker. Single-cell RNA sequencing (scRNA-seq) revealed 11 distinct clusters including mature tenocyte population and tenogenic differentiation trajectory, which well recapitulates in vivo developmental process. Dataset of scRNA-seq and transcriptome of Scx deficient tendon enabled identification of Scx-related genes in which tendon-related genes are enriched. Collectively, this study leads to a new opportunity for tendon research and provides further insight into mechanistic understanding of the differentiation pathway to a tenogenic fate.
2022-03-09 | GSE168451 | GEO
Project description:GDF5 is a potent tenogenic differentiation inducer. We previously demonstrated that GDF5 induced in vitro tenogenesis of human bone marrow-derived stromal cells (hMSC). We used microarrays to detail the global gene expression profiles underlying tenogenesis and identified distinct classes of up-regulated genes during this process.
2017-02-11 | GSE55027 | GEO
Project description:Bone defects in the craniofacial region, such as mandibular critical-sized defects (CSDs), represent a significant clinical challenge due to the limited self-healing capacity and shortcomings of current therapeutic options. Bone tissue engineering using human adipose-derived stem cells (hASCs) offers a promising alternative. This study investigates the role of histone deacetylase 4 (HDAC4) and its inhibition as a therapeutic strategy in regulating hASCs osteogenic differentiation via histone acetylation. Using CUT&Tag sequencing, we identified HDAC4-regulated histone acetylation sites that modulate the expression of osteogenesis-related factors, including the key transcription factor SMAD4. HDAC4 knockdown enhanced histone acetylation, promoted SMAD4 expression, and significantly improved osteogenic differentiation of hASCs. These findings were further validated in vivo using calvarial and mandibular defect models in nude mice. As an alternative inhibition strategy, the selective HDAC4 inhibitor Tasquinimod (Tasq) was evaluated. At 1 µM, Tasq enhanced hASCs proliferation, promoted histone acetylation, upregulated SMAD4, and stimulated osteogenic differentiation markers (ALP, OSX, COL1A1), mimicking the effects of HDAC4 knockdown. To enable localized delivery, a Tasq-loaded GelMA-F127 composite hydrogel was developed. This hydrogel exhibited excellent mechanical properties, biocompatibility, and sustained release. Applied to mandibular defects, GelMA-F127-Tasq significantly enhanced bone regeneration. In conclusion, this study elucidates the epigenetic mechanisms of HDAC4 in hASCs osteogenesis and highlights the potential of Tasq-loaded hydrogels as a therapeutic strategy for bone defect repair.
2026-07-29 | GSE308788 | GEO
Project description:This study presents a single-cell RNA sequencing (scRNAseq) analysis of six carcinosarcomas and two normal endometrial samples, profiling over 96,000 cells. By integrating transcriptomic data with inferred copy number variations (CNVs), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH), we resolve the complex cellular architecture and differentiation dynamics of these tumors. We identify distinct lineage-specific programs and uncover heterologous differentiation trajectories—including rhabdomyogenic, osteogenic, and a previously undescribed tenogenic lineage defined by SCX, MKX, and TNMD expression. Our results reveal that carcinosarcomas exhibit multilineage plasticity within their mesenchymal component and highlight the power of single-cell analysis to refine tumor classification and uncover hidden developmental programs.
2025-10-28 | GSE299623 | GEO
Project description:Critical-sized bone defects resulting from tumors, trauma, or surgery present a significant clinical challenge due to its poor self-regenerating capabilities and limited therapeutic options. Mesenchymal stem cells (MSCs) have shown promise in bone regeneration, possibly mediated through their secretion of bioactive factors rather than direct engraftment and differentiation. MSC-derived extracellular vesicles (EVs) deliver micro-RNAs (miRs), proteins and lipids that may modulate bone regeneration. EVs were isolated by differential ultracentrifugation from osteogenically induced human adipose tissue-derived MSCs (hASCs), treated with or without the small molecule SB431542, an inhibitor of TGFß-signaling (EV-hASCs[-/+]SB). EVs were characterized using Western Blot and Nanoparticle Tracking Analysis. hASCs were cultured with EV-hASCs[-/+]SBs to assess bone regeneration in vitro. Bone regeneration was assessed in vivo in calvarial defects treated with (EV-hASCs[-/+]SB). EV content was analyzed via miR-analysis and gain- and loss-of-function transfection assays were performed with identified miR. Enhanced osteogenesis is shown in vitro and in vivo upon treatment with EV-hASCs[+]SB. EV-hASCs[-/+]SB-enriched miR-20a-5p was identified as a modulating factor in osteogenesis, silencing BAMBI and enhancing early downstream phosphorylation of SMAD1/5 and late activation of ß-Catenin in ASCs undergoing osteogenic differentiation, targets of BMP- and Wnt-signaling pathways. EVs act as carriers for miR-mediated paracrine signaling, harnessing the therapeutic potential of MSCs, while circumventing the high immunogenicity and risk of neoplastic transformation associated with cell-based therapies.
2026-04-30 | GSE286905 | GEO
Project description:Single cell RNA sequencing analysis of stem cells after tenogenic differentiation
| PRJNA1469490 | ENA