3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA774268 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Understanding the molecular underpinnings of adipogenesis is of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold-free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi-omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R^2 = 0.97). Integration of multi-omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis.
2021-10-27 | GSE186519 | GEO
Project description: Not available
| S-EPMC8373086 | biostudies-literature
Project description:Liver models that closely mimic the in vivo microenvironment are central for understanding liver functions, capabilities, and intercellular communication processes. Whereas hepatocyte monolayers de-differentiate after only a few days in culture, constructs consisting of hepatocytes and non-parenchymal cells (NPC) separated by a polyelectrolyte multilayer (PEM) provide maintenance of hepatic phenotypes. To better understand the mechanisms and processes that underlie organotypic liver model function, hepatocyte protein abundances in the presence and absence of liver sinusoidal endothelial cells (LSECs) were compared to hepatocyte monolayers. The presence of the PEM led to increases in proteins associated with hepatocyte lipid metabolism, with mitochondrial-based β-oxidation and peroxisomal proteins found in higher abundance. It was also demonstrated that the presence of LSECs modulates levels of carboxylesterases and other phase I and phase II enzymes. These results are discussed in relation to intercellular signaling and hepatocyte function.
2017-07-06 | PXD002491 | Pride
Project description:Colorectal and pancreatobiliary cancers are the most common digestive cancers. Their incidence has particularly increased over the last few decades, leading to suspicion that environmental factors are involved. In addition, strategies for the therapeutic management of these cancers are evolving in the context of the development of immunotherapies.
Tumor microenvironment is a potential source of new diagnostic, prognostic and predictive markers and new therapeutic targets. The links between tumor microenvironment and modulation of the immune system in colorectal and pancreatobiliary cancers are poorly understood. Molecular classifications have been proposed for these cancers, but their link with immunity and response to treatment remains to be explored.
Objective : explore links between molecular subtypes, tumor microenvironment, host (immune system, pre-metastatic niche, intestinal microbiota, metabolism), and survival (prognostic value), response (predictive value) and tolerance (toxicities) to treatments in digestive cancers, in particular colorectal and pancreatobiliary cancers.
Method: Retrospective and prospective monocentric cohort study
| 2363741 | ecrin-mdr-crc
Project description:Refined cancer models are required to assess the burgeoning number of potential targets for cancer therapeutics within a rapid and clinically relevant context. Here we utilize tumor-associated genetic pathways to transform primary human epithelial cells from epidermis, oropharynx, esophagus, and cervix into genetically defined tumors within an entirely human 3-dimensional (3-D) tissue environment incorporating cell-populated stroma and intact basement membrane (BM). These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through the BM, a complex process critically required for biologic malignancy in 90% of human cancers. Invasion was rapid, and potentiated by stromal cells. Oncogenic signals in 3-D tissue, but not 2-D culture, resembled gene expression profiles from spontaneous human cancers. Screening well-characterized signaling pathway inhibitors in 3-D organotypic neoplasia helped distil a clinically faithful cancer gene signature. Multi-tissue 3-D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterize cancer progression. Organotypic human cervical epithium expressing LacZ, cdk4 and Ras, or cdk and Ras with U0126 mediated MEK inhibition were harvested for RNA extraction and hybridization on Affymetrix microarrays. There are 2 biologic replicates for each group.
2010-09-15 | E-GEOD-22382 | biostudies-arrayexpress
Project description:White adipocytes function as the major energy reservoir in humans by storing large amounts of triglycerides. Their dysfunction is associated with metabolic disorders. However, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generated a spatiotemporal proteomic atlas of human adipogenesis to gain insights into cellular remodeling and the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation. Our study highlights the coordinated regulation of protein localization and abundance during adipogenesis. More specifically, we identified a compartment-specific regulation of protein levels to reprogram branched chain amino acid and one-carbon metabolism to provide building blocks and reduction equivalents for lipid synthesis. Additionally, we identified C19orf12 as a differentiation induced adipocyte-specific lipid droplet (LD) protein, which interacts with the translocase of the outer membrane (TOM) complex of LD associated mitochondria and modulates adipocyte lipid storage. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.
2024-01-17 | PXD047412 | Pride
Project description:Keratinocyte ethnicity affects transcriptomic response of human organotypic raft cultures
2021-03-01 | GSE163711 | GEO
Project description:Refined cancer models are required to assess the burgeoning number of potential targets for cancer therapeutics within a rapid and clinically relevant context. Here we utilize tumor-associated genetic pathways to transform primary human epithelial cells from epidermis, oropharynx, esophagus, and cervix into genetically defined tumors within an entirely human 3-dimensional (3-D) tissue environment incorporating cell-populated stroma and intact basement membrane (BM). These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through the BM, a complex process critically required for biologic malignancy in 90% of human cancers. Invasion was rapid, and potentiated by stromal cells. Oncogenic signals in 3-D tissue, but not 2-D culture, resembled gene expression profiles from spontaneous human cancers. Screening well-characterized signaling pathway inhibitors in 3-D organotypic neoplasia helped distil a clinically faithful cancer gene signature. Multi-tissue 3-D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterize cancer progression.
2010-09-15 | GSE22382 | GEO
Project description:The blockage of GABA-A ionotropic channels by means of gabazine is a widespread model of plasticity where the increased synaptic activity triggered by Gabazine leads to the up-regulation of a plethora of activity-dependent genes. Here, we sought to characterize the overall transcriptional response of GABA-A blocking of rat hippocampal organotypic cultures. In each of the three biological replica, half of the organotypic hippocampal cultures derived from two rat littermates were treated with gabazine and compared to the untreated ones in order to determine the set of differentially expressed genes.
2013-05-14 | E-GEOD-46864 | biostudies-arrayexpress
Project description:The blockage of GABA-A ionotropic channels by means of gabazine is a widespread model of plasticity where the increased synaptic activity triggered by Gabazine leads to the up-regulation of a plethora of activity-dependent genes. Here, we sought to characterize the overall transcriptional response of GABA-A blocking of rat hippocampal organotypic cultures.
2013-05-14 | GSE46864 | GEO