Does osteogenic potential of clonal human bone marrow mesenchymal stem/stromal cells correlate with their vascular supportive ability?
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ABSTRACT:
PROVIDER: PRJNA483407 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7618880.fastq.gz | Fastqsanger.gz | |||
| SRR7618890.fastq.gz | Fastqsanger.gz | |||
| SRR7618881.fastq.gz | Fastqsanger.gz | |||
| SRR7618882.fastq.gz | Fastqsanger.gz | |||
| SRR7618883.fastq.gz | Fastqsanger.gz |
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Project description:Human bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing and potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products (ATMPs) for cellular therapies. Since the healing of bone defects in larger bone grafts depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist. We tested this by assessing the lineage (i.e. adipogenic {A}, osteogenic {O} and/or chondrogenic {C}) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic {O} potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses. Our results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent. RNAseq of individual clones defined gene fingerprints relevant to this correlation.
2018-12-26 | GSE117844 | GEO
Project description:BackgroundHuman bone marrow-derived mesenchymal stem/stromal cells (hBM MSCs) have multiple functions, critical for skeletal formation and function. Their functional heterogeneity, however, represents a major challenge for their isolation and in developing potency and release assays to predict their functionality prior to transplantation. Additionally, potency, biomarker profiles and defining mechanisms of action in a particular clinical setting are increasing requirements of Regulatory Agencies for release of hBM MSCs as Advanced Therapy Medicinal Products for cellular therapies. Since the healing of bone fractures depends on the coupling of new blood vessel formation with osteogenesis, we hypothesised that a correlation between the osteogenic and vascular supportive potential of individual hBM MSC-derived CFU-F (colony forming unit-fibroblastoid) clones might exist.MethodsWe tested this by assessing the lineage (i.e. adipogenic (A), osteogenic (O) and/or chondrogenic (C)) potential of individual hBM MSC-derived CFU-F clones and determining if their osteogenic (O) potential correlated with their vascular supportive profile in vitro using lineage differentiation assays, endothelial-hBM MSC vascular co-culture assays and transcriptomic (RNAseq) analyses.ResultsOur results demonstrate that the majority of CFU-F (95%) possessed tri-lineage, bi-lineage or uni-lineage osteogenic capacity, with 64% of the CFU-F exhibiting tri-lineage AOC potential. We found a correlation between the osteogenic and vascular tubule supportive activity of CFU-F clones, with the strength of this association being donor dependent. RNAseq of individual clones defined gene fingerprints relevant to this correlation.ConclusionsThis study identified a donor-dependent correlation between osteogenic and vascular supportive potential of hBM MSCs and important gene signatures that support these functions that are relevant to their bone regenerative properties.
| S-EPMC6300038 | biostudies-literature
Project description:Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage. Clonal MSC were selected on the basis of CD146 level at their surface (CD146Low and CD146 High) and non-clonal MSC were compared from 4 different donors.
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2023-11-22 | GSE243752 | GEO
Project description:Bone-marrow mesenchymal stem cells (MSCs) are plastic adherent cells that can differentiate into various tissue lineages, including osteoblasts, adipocytes and chondrocytes. However, this progenitor property is not shared by all cells within the MSC population. In addition, MSCs vary in their proliferation capacities and expression of markers. Because of heterogeneity of CD146 expression in the MSC population, we compared CD146-/Low and CD146High cells under clonal and non-clonal (sorted MSCs) conditions to determine whether this expression is associated with specific functions. CD146-/Low and CD146High MSCs did not differ in colony-forming unit-fibroblast number, osteogenic and adipogenic differentiation or in vitro hematopoietic supportive activity. However, CD146-/Low clones proliferated slightly but significantly faster than did CD146High clones. In addition, a strong expression of CD146 molecule was associated with a commitment towards a vascular smooth muscle cell lineage with upregulation of calponin-1 expression. Thus, within a bone-marrow MSC population, certain subpopulations characterized by high expression of CD146, are committed toward a vascular smooth muscle cell lineage.
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Project description:Chromodomain helicase DNA-binding protein 7 (CHD7) is an ATP-dependent chromatin remodeling enzyme, functioning as chromatin reader to conduct epigenetic modification. Its effect on osteogenic differentiation of human dental follicle cells (hDFCs) remains unclear. Here we show CHD7 expression increases with osteogenic differentiation. knockdown of CHD7 impairs the osteogenic ability of hDFCs, characterized by reduced alkaline phosphatase activity and mineralization, and decreased expression of osteogenesis-related genes. Conversely, CHD7 overexpression enhances the osteogenic differentiation of hDFCs. Mechanically, RNA-seq analyses revealed the down-regulated enrichment of PTH (parathyroid hormone)/PTH1R (parathyroid hormone receptor-1) signaling pathway after CHD7 knockdown. We found the expression of PTH1R positively correlates with CHD7. Importantly, overexpression of PTH1R in CHD7-knockdown hDFCs partially rescued the impaired osteogenic differentiation. Our research demonstrates that CHD7 regulates the osteogenic differentiation of hDFCs by regulating the transcription of PTH1R.
2020-07-22 | GSE154822 | GEO
Project description:Growth, remodeling, adaptation and repair of bone is critically dependent on the ability of tissue resident progenitors to differentiate into and thereby renew parenchymal cells of the osteoblast, chondrocyte, and adipocyte lineage. We recently reported that the activation of osteoblast-selective genes, such as alkaline phosphatase (ALPL), occurs through activation of pre-established enhancers, i.e., regulatory regions bound by transcriptional regulators prior to osteogenic induction. Using mass spectrometry-based quantitative proteomics, we identified 324 proteins with lineage-specific association to putative ALPL enhancer sequences during early osteoblast and adipocyte differentiation. Barrier to autointegration protein 1 (BANF1), known to be involved in chromatin compression and mutated in the Nestor-Guillermo progeria syndrome, was identified as a factor binding ALPL enhancers in an osteogenesis-selective manner. Using ChIP-seq analysis, we show here that BANF1associates with both structural and regulatory elements of the chromatin landscape in stromal cells and that BANF1 bound regulatory elements and nearby genes show increased activity upon osteogenic differentiation. Modulating BANF1 protein levels, first, alters expression of genes with nearby BANF1 binding, and second, strongly correlates with WNT signaling, osteogenic differentiation and bone forming capacity of the cells. Finally, genetic data reveal that the BANF1 locus harbors human sequence variations that correlate changes in bone mineral density and BANF1 expression while expression data from human bone related biopsies link decreased BANF1 expression with aging and osteoporosis. In conclusion, we identified BANF1 as a strong pro-osteogenic factor that is necessary for the maintenance of a cellular and molecular signature of osteoblast activity and bone formation in vivo.
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