Chidamide suppresses adipogenic differentiation of bone marrow derived mesenchymal stem cells
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ABSTRACT:
PROVIDER: PRJNA820040 | ENA |
REPOSITORIES: ENA
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Project description:To explore the potential mechanism of chidamide in BM-MSC-mediated adipogenesis, we have employed mRNA microarray expression profiling platform to identify significant differential genes associated with adipogenic differentiation and chidamide management.
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Project description:Bone marrow stromal cells (BMSCs) were isolated from the femora and tibiae of irtTA-GBD*-TAg transgenic mice. Using cellular cloning we established skeletal progenitors with unipotent osteogenic and adipogenic properties. Previous RNA-seq analysis of more progenitor types revealed differential expression in members of the Interferon-gamma (IFNγ) signaling pathway. Treatment of adipogenic progenitors with IFNγ inhibited adipogenesis and promoted osteogenesis. RNA-seq analysis of osteogenic, adipogenic and IFNγ treated adipogenic clones revealed factors controlling the osteogenic versus adipogenic commitment of bone marrow skeletal progenitors.
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Project description:Bone marrow mesenchymal stromal cells (MSCs) constitute one of the important components of the hematopoietic microenvironmental niche. There is in vitro evidence that marrow MSCs are able to support leukemia progenitor cell proliferation and survival and provide resistance to cytotoxic therapies. How MSCs from leukemia marrow differ from normal counterparts and how they are influenced by the presence of leukemia stem, and progenitor cells are still incompletely understood. In this work, we compared normal donor (ND) and acute myelogenous leukemia (AML) derived MSCs and found that AML-MSCs had increased adipogenic potential with improved ability to support survival of leukemia progenitor cells. To identify underlying changes, RNA-Seq analysis was performed. Gene ontology and pathway analysis revealed adipogenesis to be among the set of altered biological pathways dysregulated in AML-MSCs as compared to ND-MSCs. Expression of both SOX9 and EGR2 was decreased in AML-MSCs as compared to ND-MSCs. Increasing expression of SOX9 decreased adipogenic potential of AML-MSCs and decreased their ability to support AML progenitor cells. These findings suggest that AML-MSCs possess adipogenic potential which may enhance support of leukemia progenitor cells.
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Project description:To further reveal key mRNAs deciding osteogenic, adipogenic, and chondrogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in early phases, we have employed next-generation high-throughput transcriptome sequencing to detect the expression of mRNA in rat BMSCs during differentiation.
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Project description:Radiation causes a collapse of bone marrow cells and elimination of microvasculature. Bone marrow has a limited regenerative ability and the mechanism governing such recovery is largely unknown. Mesenchymal lineage cells provide supportive microenvironment for hematopoiesis and angiogenesis in bone. We recently discovered a non-proliferative mesenchymal subpopulation, marrow adipogenic lineage precursors (MALPs), that express most adipogenic markers with no lipid accumulation. To investigate the acute radiation effects, we performed single cell RNA-sequencing (scRNA-seq) on bone marrow mesenchymal lineage cells at day 3 after focal radiation. Interestingly, computational analysis revealed that MALPs become highly proliferative and acquire myofibroblast features after radiation. Using an adipocyte-specific Adipoq-Cre to label MALPs in vivo, we found that radiation indeed rapidly and transiently expands MALPs. MALPs have a cell body with multiple cell processes that form a 3D network inside bone marrow. Shortly after radiation, MALPs lost most of cell processes, became more elongated, and highly expressed myofibroblast-related genes, coinciding with marrow vessel dilation and diminished bone marrow cellularity. Later when vessels and hematopoietic cells recovered, MALPs returned to the baseline number and a normal reticular shape. Ablation of MALPs completely blocked the recovery of bone marrow vasculature and cellularity, including hematopoietic stem and progenitors. MALPs highly express several hematopoietic and angiogenic factors. Depleting one of them, VEGFa, specifically in MALPs, delayed bone marrow recovery after radiation. Taken together, our research demonstrates a critical role of MALPs in mediating the marrow repair after radiation injury and sheds light on a new cellular target for treating marrow suppression after radiotherapy.
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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:Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells (MSCs), the true identity of MSCs and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined MSCs and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a new component of marrow adipose tissue.
2020-05-01 | GSE145477 | GEO
Project description:In bone marrow, mesenchymal stromal cells (BMSCs), the precursors of adipocytes and osteoblasts, are exposed to a plethora of stimuli that determine the balance between adipogenesis and osteogenesis which in turn are competing and reciprocal. The differentiation of BMSCs, in fact, is a two-step process, lineage commitment (from MSCs to lineage-specific pro-genitors) and maturation (from progenitors to specific cell types). Adipogenesis is a finely tuned multi-step process requiring the sequential activation of numerous transcription factors driving the typical physiological and morphological changes observed in the progenitor cells, i.e., cell cycle arrest, metabolic reprogramming, and lipid accumulation. Among the small non-coding RNAs, microRNAs represent an additional mechanism for controlling adipogenic gene expression. Given their unique ability to simultaneously regulate multiple protein targets and processes, it has been suggested that microRNAs may play a leading role in BMSC differentiation. Here, we evaluated miRNAs differentially regulated during human BMSC adipogenic differentiation in vitro.
2021-12-01 | GSE189508 | GEO
Project description:Terminal differentiation of multipotent stem cells is achieved through a coordinated cascade of activated transcription factors and epigenetic modifications that drive gene transcription responsible for unique cell fate. Within the mesenchymal lineage, factors such as RUNX2 and PPARγ are indispensable for osteogenesis and adipogenesis, respectively. We therefore investigated genomic binding of transcription factors and accompanying epigenetic modifications that occur during osteogenic and adipogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (MSC). As assessed by ChIP-seq and RNA-seq analyses, we found that genes vital for osteogenic identity were linked to RUNX2, C/EBPβ, RXR, and VDR binding sites, whereas adipocyte differentiation favored PPARγ, RXR, C/EBPα, and C/EBPβ binding sites. Epigenetic marks were clear predictors of active differentiation loci as well as enhancer activities and selective gene expression. These marrow-derived MSCs displayed an epigenetic pattern that suggested a default preference for the osteogenic pathway; however, these patterns were rapidly altered near the Adipoq, Cidec, Fabp4, Lipe, Plin1, Pparg and Cebpa genes during adipogenic differentiation. Surprisingly, we found that these cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice-versa) after commitment, as assessed by staining, gene expression, and ChIP-qPCR analysis. The osteogenic default pathway may be subverted during pathological conditions leading to skeletal fragility and increased marrow adipocity during aging, estrogen deficiency and skeletal unloading. Taken together, our data provide an increased mechanistic understanding of the epigenetic programs necessary for multipotent differentiation of MSCs that may prove beneficial in the development of therapeutic strategies.
2016-07-11 | GSE79814 | GEO