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The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells [ATAC-seq]

ABSTRACT: Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, and skin fibroblasts (FB). We assessed uniquely accessible enhancers facilitating bone regeneration potential.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182496 | GEO | 2023/04/03

REPOSITORIES: GEO

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The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells [ChIP-seq]

Project description:Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, chondrocytes (CH) and skin fibroblasts (FB). We assessed active regulatory regions facilitating bone-regeneration potential.

2023-04-03 | GSE182495 | GEO

Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

Project description:Despite similarities in morphology, phenotype and in vitro behavior, Mesenchymal Stromal Cells (MSC) form various tissue sources show striking differences in their in vivo potential to form bone, cartilage and hematopoietic support tissue. Comparing four commonly use MSC sources (bone marrow (BM), white adipose tissue (WAT), umbilical cord (UC) and skin) we found only bone marrow (BM)-derived MSCs capable of endochondral ossification and marrow attraction. To gain mechanistic insights explaining this differences we analyzed gene expression characteristics of MSC from all four tissue sources using Affymetrix Genechip Human Gene 2.0 ST Array. MSCs from BM, WAT, UC and skin were isolated using plastic adherence. Cells were expanded in standard alpha-MEM supplemented with pooled human platelet lysate fully replacing fetal bovine serum. MSCs were subcutaneously implanted into immune-compromised mice to comparatively evaluate bone formation and subsequent bone marrow attraction. In parallel we have isolated RNA from all sources to analyze tissue source specific gene expression profile.

2014-04-30 | E-GEOD-57151 | biostudies-arrayexpress

Epigenetic and in vivo comparison of diverse mesenchymal stromal cell sources reveals an endochonrdal signature for human hematopoietic niche formation

2014-04-30 | GSE57151 | GEO

Human bone and marrow niche formation by mesenchymal progenitors in vivo is predefined by an organotypic epigenetic signature

Project description:In this study, we have analyzed DNA methylation characteristics of human mesenchymal stem and progenitor cells (MSPCs) form different tissue sources including bone marrow (BM), white adipose tissue (WAT ), umbilical cord (UC) as well as dermal fibroblasts by using the HumanMethylation450K array. Cells able to form bone through endochondral ossification and attract bone marrow in an innovative in vivo model were compared to cells lacking these capacities. Interestingly only BM-derived MSPCs were capable of bone formation and marrow attraction. These features correlated with unique epigenetic characteristics potentially enabling BM-derived cells to undergo endochondral ossification. 12 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2015-02-04 | E-GEOD-41933 | biostudies-arrayexpress

Human bone and marrow niche formation by mesenchymal progenitors in vivo is predefined by an organotypic epigenetic signature

2015-02-04 | GSE41933 | GEO

β-NGF promotes cartilage to bone conversion, accelerating endochondral fracture repair

Project description:During endochondral fracture repair, a myriad of biochemical and phenotypic changes occur at the chondro-osseuous junction that regulate cartilage to bone conversion. Osteogenic and angiogenic factors have long been studied for accelerating fracture repair. In our concise study, we focused on the neurotrophic factor nerve growth factor (NGF) and its receptor tropomyosin receptor kinase A (TRKA) as understudied therapeutic targets for accelerating endochondral fracture repair. We first characterized endogenous expression of NGF and TRKA during endochondral repair of tibial fractures. We then analyzed gene expression data from β-NGF stimulated hypertrophic cartilage and observed a promotion in endochondral ossification associated markers. Additional gene ontology analyses revealed promotion of genes associated with Wnt activation, PDGF binding, and integrin binding. Subsequent histological analyses of in vivo samples confirmed Wnt activation following local β-NGF injections via reporter mice. Finally, we tested the therapeutic efficacy of local β-NGF injections in mice, which resulted in a decrease of cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate the ability for β-NGF to promote endochondral fracture repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during endochondral ossification.

2020-12-22 | GSE150092 | GEO

Homo sapiens

Project description:Engineering endochondral ossification using Sonic Hedgehog for bone regeneration

| PRJNA127409 | ENA

Mesenchymal Stem Cells (MSCs) Alleviate Experimental Immune-mediated Liver Injury via Chitinase 3-like protein 1-mediated T cell suppression

Project description:RNA-seq for MSCs from human bone marrow (BM-MSCs), olfactory mucosa (OM-MSCs), and umbilical cord (UC-MSCs) (2 donors for each). RNA-sequencing for human naïve CD3+ T cells, CD3+ T cells activated with PHA (2.5 μg/mL) for 48 h， and CD3+ T cells co-cultured with human UC-MSCs in the presence of PHA for 48 h.

2021-02-09 | GSE166327 | GEO

Delineating the heterogeneity of matrix-directed differentiation towards soft and stiff tissue lineages via single-cell profiling.

Project description:Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent progenitors that contribute to tissue regeneration and homeostasis. MSCs assess extracellular elasticity by probing resistance to applied forces via adhesion, cytoskeletal, and nuclear mechanotransducers, that direct differentiation toward soft or stiff tissue lineages. Even under controlled conditions, MSC differentiation exhibits substantial cell-to-cell variation that remains poorly characterized. By single-cell transcriptional profiling of naïve, matrix-conditioned, and early differentiation state cells, we identified distinct MSC subpopulations with distinct mechanosensitivities, differentiation capacities, and cell cycling. We showed that soft matrices support adipogenesis of multipotent cells and endochondral ossification of non-adipogenic cells, whereas intramembranous ossification and pre-osteoblast proliferation are enhanced by stiff matrices. Using diffusion pseudotime mapping, we delineated hierarchical matrix-directed differentiation and identified mechanoresponsive genes. We found that tropomyosin-1 (TPM1) is highly sensitive to stiffness cues both at RNA and protein levels and that changes in expression of TPM1 determine adipogenic or osteogenic fates. Thus, cell-to-cell variation in tropomyosin-mediated matrix-sensing contributes to impaired differentiation with implications to the biomedical potential of MSCs.

2021-05-01 | GSE166824 | GEO

Engineering endochondral ossification using Sonic Hedgehog for bone regeneration

Project description:Endochondral ossification (EO) is the natural route for the regeneration of large and mechanically challenged bone defects. Regeneration occurs via a fibrocartilagenous phase which turns into bone upon vascularization and the formation of a transient collagen type X extra cellular matrix. These two critical initiator of EO are mediated by Hedgehog proteins. We investigated a tissue engineering approach using Sonic Hedgehog (Shh) as a pleiotropic factor regulating the in vitro formation of a vascularized bone tissue precursor for in vivo endochondral bone formation. The tissue engineered graft was formed using human mesenchymal stem cells and prevascularized using human umbilical vein endothelial cells. We show that Shh induced, in vitro, the maturation of the engineered vascular network along with the expression of collagen type X which resulted, in vivo, in an improved vascularization and the rapid formation of large amounts of osteoids through EO. Osteoids further matured into, currently unmatched, clinically relevant amount of lamellar bone including osteoclasts, bone lining cells and bone marrow-like cavities. This result suggests that Hh is a master regulator of EO allowing for the formation of complex tissues with considerable therapeutic potential for bone regeneration. The effect of Cyclopamine on expression of Hedgehog, angiogenesis and axon guidance marker genes was analyzed by seeding a coculture of 92% hMSCs and 8% huvEC supplemented or not in cyclopamine, for 12 days

2012-09-01 | E-GEOD-22293 | biostudies-arrayexpress

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