In Vitro Mesenchymal Stem Cell Differentiation Landscape
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241130 | GEO | 2024/05/17
REPOSITORIES: GEO
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Project description:Pathological processes like osteoporosis or steroid-induced osteonecrosis of the hip are accompanied by increased bone marrow adipogenesis. Such disorder of adipogenic/osteogenic differentiation, which affects also bone marrow derived mesenchymal stem cells (BMSCs) contributes to bone loss during aging. Therefore, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on osteogenic and adipogenic differentiation capacity of naïve hBMSCs.
2022-10-14 | PXD035845 | Pride
Project description:Osteogenic differentiation of human mesenchymal stromal cells (hMSCs) may potentially be used in cell-based bone tissue-engineering applications to enhance the bone-forming potential of these cells. Osteogenic differentiation and adipogenic differentiation are thought to be mutually exclusive, and although several signaling pathways and cues that induce osteogenic or adipogenic differentiation, respectively, have been identified, there is no general consensus on how to optimally differentiate hMSCs into the osteogenic lineage. Some pathways have also been reported to be involved in both adipogenic and osteogenic differentiation, as for example, the protein kinase A (PKA) pathway, and the aim of this study was to investigate the role of cAMP/PKA signaling in differentiation of hMSCs in more detail. We show that activation of this pathway with dibutyryl-cAMP results in enhanced alkaline phosphatase expression, whereas another cAMP analog induces adipogenesis in long-term mineralization cultures. Adipogenic differentiation, induced by 8-bromo-cAMP, was accompanied by stronger PKA activity and higher expression of cAMP-responsive genes, suggesting that stronger activation correlates with adipogenic differentiation. In addition, a whole-genome expression analysis showed an increase in expression of adipogenic genes in 8-br-cAMP-treated cells. Furthermore, by means of quantitative polymerase chain reaction, we show differences in peroxisome proliferator-activated receptor-gamma activation, either alone or in combination with dexamethasone, thus demonstrating differential effects of the PKA pathway, most likely depending on its mode of activation.
2018-08-05 | E-MTAB-7038 | biostudies-arrayexpress
Project description:Physical activity improves overall health and counteracts metabolic pathologies. Adipose tissue and bone are important key targets of exercise; the prevalence of diseases associated with suboptimal physical activity levels has increased in recent times as a result of lifestyle changes. Mesenchymal stem cells (MSCs) differentiation in either osteogenic or adipogenic lineage is regulated by many factors. Particularly, the expression of master genes such as RUNX2 and PPARγ2 is essential for MSC commitment to osteogenic or adipogenic differentiation, respectively. Besides various positive effects on health, some authors have reported stressful outcomes as a consequence of endurance in physical activity. We looked for further clues about MSCs differentiation and serum proteins modulation studying the effects of half marathon in runners by means of gene expression analyses and a proteomic approach. Our results demonstrated an increase in osteogenic commitment and a reduction in adipogenic commitment of MSCs. In addition, for the first time we have analyzed the proteomic profile changes in runners after half-marathon activity in order to survey the related systemic adjustments. Interestingly, proteomic data showed the activation of both inflammatory response and detoxification process. Moreover, the involvement of pathways associated to immune response, lipid transport and coagulation, was elicited. Notably, positive and negative effects may be strictly linked.
2017-09-25 | PXD006704 | Pride
Project description:Gene Expression analysis of a differentiation timeseries of human Mesenchymal Stem Cells (hMSCs) in the presence of adipogenic/osteogenic factors. hMSCs differentiate into fat cells when treated with dexamethasone (10^-6 M), insulin (10 ug/ml), rosiglitazone (10^-7 M) and IBMX (250 uM). TGFbeta (5 ng/ml) inhibits this process and redirects these cells to differentiate into bone cells. Introduction: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. Methods: In order be able to interfere with this process, we have investigated in vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted. By means of gene expression microarray analysis, we have investigated genes which are potential targets for prevention of fat cell differentiation. Results: Our data show that BMP2 promotes both adipogenic and osteogenic differentiation of hMSCs, while TGFβ inhibits differentiation into both lineages. However, when cells are cultured under adipogenic differentiation conditions, which contains cAMP-enhancing agents such as IBMX of PGE2, TGFβ promotes osteogenic differentiation, while at the same time inhibiting adipogenic differentiation. Gene expression and immunoblot analysis indicated that cAMP-induced suppression of HDAC5 levels plays an important role in the inhibitory effect of TGFβ on osteogenic differentiation. By means of gene expression microarray analysis, we have investigated genes which are downregulated by TGFβ under adipogenic differentiation conditions and may therefore be potential targets for prevention of fat cell differentiation. We thus identified 9 genes for which FDA-approved drugs are available. Our results show that drugs directed against the nuclear hormone receptor PPARG, the metalloproteinase ADAMTS5 and the aldo-keto reductase AKR1B10 inhibit adipogenic differentiation in a dose-dependent manner, although in contrast to TGFβ they do not appear to promote osteogenic differentiation. Conclusions: The approach chosen in this study has resulted in the identification of new targets for inhibition of fat cell differentiation, which may not only be relevant for prevention of osteoporosis, but also of obesity. hMSCs were induced to differentiate in the presence dexamethasone, insulin and rosiglitazone, to which was added either 50 ng/ml BMP2; BMP2 + TGFbeta; BMP2 + IBMX; BMP2 + TGFbeta + IBMX.
2016-07-19 | E-GEOD-84500 | biostudies-arrayexpress
Project description:Background: Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition. Methodology/Principal findings: Our aim was to analyze the dynamics of differentiation of two closely related stromal cell types, adipose tissue-derived MSCs and dermal fibroblasts (FBs) along adipogenic, osteogenic and chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated donor-matched MSCs and FBs are distinct populations that stay different upon differentiation into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression occur early in differentiation and persist over time in both MSCs and FBs. Further, MSCs and FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation. Conclusion: Our findings suggest that stromal stem cells including adipose-derived MSCs and dermal FBs exploit different molecular mechanisms of differentiation to reach a common cell fate. The early mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation between MSCs and FBs. A total of 91 samples were analyzed by multiplex RNA-seq. Samples represented replicates from two patients, two cell types and three differentiation protocols, as indicated by the sample annotation. 5 barcodes were unused, but the corresponding FASTQ files are included for completeness.
2012-06-27 | E-GEOD-37521 | biostudies-arrayexpress
Project description:Background: Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition. Methodology/Principal findings: Our aim was to analyze the dynamics of differentiation of two closely related stromal cell types, adipose tissue-derived MSCs and dermal fibroblasts (FBs) along adipogenic, osteogenic and chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated donor-matched MSCs and FBs are distinct populations that stay different upon differentiation into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression occur early in differentiation and persist over time in both MSCs and FBs. Further, MSCs and FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation. Conclusion: Our findings suggest that stromal stem cells including adipose-derived MSCs and dermal FBs exploit different molecular mechanisms of differentiation to reach a common cell fate. The early mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation between MSCs and FBs.
2012-06-28 | GSE37521 | GEO
Project description:Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation while stimulating the migration, in vitro and in vivo, of human bone marrow-derived mesenchymal stem cells (BM-hMSC). Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes (e.g. wnt-pathway-related genes) governing osteoblastic and adipogenic differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenic and osteogenic differentiation by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPARγ (peroxisome proliferator activated receptor-gamma) and by promoting the mineralization and the expression of the osteoblast-related gene RUNX2 (Runt-related transcription factor 2), respectively. BM-hMSCs cells were transiently exposed to ATP 1mM for 24 hours (ATP pre-treatment) before starting differentiation induction. Then, BM-hMSCs were cultured under adipogenic/osteogenic conditions. Gene Expression Profile was performed on differentiate cells after 3 weeks of induction culture.
2013-04-11 | E-GEOD-37237 | biostudies-arrayexpress
Project description:Schittler2010 - Cell fate of progenitor cells, osteoblasts or chondrocytes
Mathematical model describing the mechanism of differentiation of mesenchymal stem cells to bone (osteoblasts) or cartilage (chondrocytes) cells.
This model is described in the article:
Cell differentiation modeled via a coupled two-switch regulatory network.
Schittler D, Hasenauer J, Allgöwer F, Waldherr S.
Chaos 2010 Dec; 20(4): 045121
Abstract:
Mesenchymal stem cells can give rise to bone and other tissue cells, but their differentiation still escapes full control. In this paper we address this issue by mathematical modeling. We present a model for a genetic switch determining the cell fate of progenitor cells which can differentiate into osteoblasts (bone cells) or chondrocytes (cartilage cells). The model consists of two switch mechanisms and reproduces the experimentally observed three stable equilibrium states: a progenitor, an osteogenic, and a chondrogenic state. Conventionally, the loss of an intermediate (progenitor) state and the entailed attraction to one of two opposite (differentiated) states is modeled as a result of changing parameters. In our model in contrast, we achieve this by distributing the differentiation process to two functional switch parts acting in concert: one triggering differentiation and the other determining cell fate. Via stability and bifurcation analysis, we investigate the effects of biochemical stimuli associated with different system inputs. We employ our model to generate differentiation scenarios on the single cell as well as on the cell population level. The single cell scenarios allow to reconstruct the switching upon extrinsic signals, whereas the cell population scenarios provide a framework to identify the impact of intrinsic properties and the limiting factors for successful differentiation.
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2024-09-02 | BIOMD0000000493 | BioModels
Project description:Gene Expression analysis of a differentiation timeseries of human Mesenchymal Stem Cells (hMSCs) in the presence of adipogenic/osteogenic factors. hMSCs differentiate into fat cells when treated with dexamethasone (10^-6 M), insulin (10 ug/ml), rosiglitazone (10^-7 M) and IBMX (250 uM). TGFbeta (5 ng/ml) inhibits this process and redirects these cells to differentiate into bone cells. Introduction: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. Methods: In order be able to interfere with this process, we have investigated in vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted. By means of gene expression microarray analysis, we have investigated genes which are potential targets for prevention of fat cell differentiation. Results: Our data show that BMP2 promotes both adipogenic and osteogenic differentiation of hMSCs, while TGFβ inhibits differentiation into both lineages. However, when cells are cultured under adipogenic differentiation conditions, which contains cAMP-enhancing agents such as IBMX of PGE2, TGFβ promotes osteogenic differentiation, while at the same time inhibiting adipogenic differentiation. Gene expression and immunoblot analysis indicated that cAMP-induced suppression of HDAC5 levels plays an important role in the inhibitory effect of TGFβ on osteogenic differentiation. By means of gene expression microarray analysis, we have investigated genes which are downregulated by TGFβ under adipogenic differentiation conditions and may therefore be potential targets for prevention of fat cell differentiation. We thus identified 9 genes for which FDA-approved drugs are available. Our results show that drugs directed against the nuclear hormone receptor PPARG, the metalloproteinase ADAMTS5 and the aldo-keto reductase AKR1B10 inhibit adipogenic differentiation in a dose-dependent manner, although in contrast to TGFβ they do not appear to promote osteogenic differentiation. Conclusions: The approach chosen in this study has resulted in the identification of new targets for inhibition of fat cell differentiation, which may not only be relevant for prevention of osteoporosis, but also of obesity.
2016-07-19 | GSE84500 | GEO
Project description:The tunica adventitia of vessels within adipose tissue (AT) represents a heterogenous microanatomical niche for multipotent mesenchymal precursor cells. To investigate this heterogeneity, cell surface antibody array among CD34+ human adventicytes identified 13 novel antigens enriched within perivascular mesenchyme, including the endolysomal associated protein CD107a (LAMP1). Membranous CD107a can be used to divide perivascular / adventitial precursor cells into functional relevant subsets. CD107alow cells from human AT demonstrated high colony forming efficiency, osteoprogenitor cell frequency, and osteogenic potential. Conversely, CD107ahigh cells demonstrated heightened adipoprogenitor cell frequency and adipogenic potential. Knockdown experiments did not identity a functional role for CD107a in osteo/adipogenic differentiation. Instead, CD107a protein trafficking to the cell surface was associated with exocytosis during early adipogenic differentiation. Bulk and single cell RNA Sequencing suggested that CD107alow cells represent a precursor population for CD107ahigh cells. Functional roles for CD107alow/high subsets were confirmed in transplantation experiments. Intramuscular transplantation of CD107alow cells yielded increased bone formation in comparison to their CD107ahigh counterparts. Further, CD107alow cells induced spine fusion whereas their CD107ahigh counterparts did not. In sum, cell surface CD107a in mesenchymal progenitors correlates with exocytosis during early adipogenesis, and can be used to divide osteo- from adipogenic progenitor cells within human fat tissue.
2020-10-06 | GSE148519 | GEO