Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer
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PROVIDER: PRJNA967346 | ENA |
REPOSITORIES: ENA
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Project description:Physical constraints like compression influence cancer cell invasion and transcriptional dynamics in various tumors. Liver cancer is characterized by the rapid proliferation of tumor cells within a densely packed tissue matrix, subjecting the cancer cells to crowding and compression. The highly dysregulated mechanical environment highlights the need to elucidate the broader impact of compression on liver cancer development and evolution. In this study, we investigated and described a unique adaptive response of liver cells to prolonged compression. Liver cells presented significant transcriptional changes due to compression, including the loss of liver-specific markers and enrichment of epithelial-to-mesenchymal transition genes. Compression elevated Rac1 activity, which promoted cellular protrusions and YAP nuclear translocation and maintained cell viability under mechanical stress. Furthermore, compression disrupted intracellular calcium signaling, leading to resistance to apoptosis. Counteracting the effects of compression by inhibiting Rac1 or manipulating intracellular calcium facilitated death of compression-adapted cells. This study highlights compression as a critical biophysical signal in the tissue microenvironment that can induce cell state transitions and disease-driving phenotypes in the liver.
2025-03-31 | GSE231717 | GEO
Project description:While biochemical regulation has been extensively studied in cerebral organoid modeling protocols, the role of mechano-regulation in directing stem cell fate and organoid development has been relatively unexplored. Volumetric compression, a key aspect of natural brain development, is known to influence neuronal differentiation. However, stiff interpenetrating network compression fails to accurately replicate the dynamic organoid development observed in nature. In this study, we present a novel method of heterogeneous embedding using an alginate-shell-Matrigel-core system. This approach allows for cell-Matrigel remodeling by the inner layer and provides moderate normal compression through the soft alginate outer layer. Our results show significant improvements in cell proliferation and maturation of cerebral organoids, as evidenced by increased expression of neuronal markers such as neurofilament (NF) and microtubule-associated protein 2 (MAP2). Compared to non-alginate embedding and alginate compression groups, volume growth remains unimpeded. Our findings demonstrate the successful mechanical regulation of cerebral organoids, which not only mimics the mechanical environment of brain development but also exhibits a regular growth profile with enhanced maturation. These results highlight the importance and potential practical applications of mechano-regulation in the establishment of brain organoids.
2023-09-09 | GSE242715 | GEO
Project description:Volumetric compression by heterogeneous scaffold embedding promotes cerebral organoid growth and maturation
| PRJNA1014410 | ENA
Project description:This SuperSeries is composed of the following subset Series: GSE37678: cDNA Microarray 1: Compression Xylem vs. Opposite Xylem GSE37736: cDNA Microarray 2: Compression Xylem vs. Opposite Xylem Refer to individual Series
2012-05-05 | E-GEOD-37789 | biostudies-arrayexpress
Project description:The within-tree variation in wood properties constitutes an exceptional model to study the mechanisms that adjust the different biosynthetic pathways providing substrates with the massive and variable demands of different biosynthetic reactions of cell wall polymers. Although a few genes have been reported as differentially expressed in differentiating compression wood compared to normal or opposite wood, the expression of a larger set of genes is expected to change due the broad range of features that distinguish this reaction wood. By combining the construction of different cDNA libraries with microarray analyses, using samples from different Pinus pinaster provenances collected in different years and geographic locations, we have identified a total of 496 genes that change their expression during differentiation of compression wood (331 up-regulated and 165 down-regulated compared to opposite wood). Consistent with the well-known structural and chemical characteristics of compression wood, a large number of genes involved in the biosynthesis of cell wall components were shown to be up-regulated during compression wood differentiation, including genes involved in synthesis of cellulose, hemicellulose, lignin and lignans. In particular, further analysis of a set of these genes involved in providing S-adenosylmethionine, ammonium recycling, lignin and lignans biosynthesis showed parallel expression profiles to levels of lignin accumulation in cells undergoing xylogenesis in vivo and in vitro. The comparative transcriptomic analysis of compression and opposite wood formation in this work have revealed a broad spectrum of coordinated transcriptional modulation of biosynthetic reactions for different cell wall polymers associated to within-tree variations in softwood structure and composition. In particular, it suggest the occurrence of a mechanism that modulates at transcriptional level genes encoding enzymes involved in S-adenosylmethionine synthesis and ammonium assimilation with coniferyl alcohol demand for lignin and lignan synthesis, as a key metabolic requirement in cells undergoing lignification. Two-condition experiment including dye-swap experiments, Compression Differentiating Xylem vs. Opposite Differentiating Xylem. Biological replicates: 4 compression xylem, 4 opposite xylew, harvested from four different individual pine trees. Two replicates per array.
2012-05-05 | E-GEOD-37678 | biostudies-arrayexpress
Project description:The within-tree variation in wood properties constitutes an exceptional model to study the mechanisms that adjust the different biosynthetic pathways providing substrates with the massive and variable demands of different biosynthetic reactions of cell wall polymers. Although a few genes have been reported as differentially expressed in differentiating compression wood compared to normal or opposite wood, the expression of a larger set of genes is expected to change due the broad range of features that distinguish this reaction wood. By combining the construction of different cDNA libraries with microarray analyses, using samples from different Pinus pinaster provenances collected in different years and geographic locations, we have identified a total of 496 genes that change their expression during differentiation of compression wood (331 up-regulated and 165 down-regulated compared to opposite wood). Consistent with the well-known structural and chemical characteristics of compression wood, a large number of genes involved in the biosynthesis of cell wall components were shown to be up-regulated during compression wood differentiation, including genes involved in synthesis of cellulose, hemicellulose, lignin and lignans. In particular, further analysis of a set of these genes involved in providing S-adenosylmethionine, ammonium recycling, lignin and lignans biosynthesis showed parallel expression profiles to levels of lignin accumulation in cells undergoing xylogenesis in vivo and in vitro. The comparative transcriptomic analysis of compression and opposite wood formation in this work have revealed a broad spectrum of coordinated transcriptional modulation of biosynthetic reactions for different cell wall polymers associated to within-tree variations in softwood structure and composition. In particular, it suggest the occurrence of a mechanism that modulates at transcriptional level genes encoding enzymes involved in S-adenosylmethionine synthesis and ammonium assimilation with coniferyl alcohol demand for lignin and lignan synthesis, as a key metabolic requirement in cells undergoing lignification. Two-condition experiment including dye-swap experiments, Compression Differentiating Xylem vs. Opposite Differentiating Xylem. Biological replicates: 4 compression xylem, 4 opposite xylew, harvested from four different individual pine trees. Two replicates per array.
2012-05-05 | E-GEOD-37736 | biostudies-arrayexpress
Project description:Volumetric Compression on Mus musculus Transcriptome
| PRJNA955120 | ENA
Project description:Compression Xylem vs. Opposite Xylem
| PRJNA163351 | ENA
Project description:We discovered mechanical compression is able to bring activated MuSCs back to their quiescent stem cell state.
2022-02-06 | GSE196101 | GEO
Project description:The within-tree variation in wood properties constitutes an exceptional model to study the mechanisms that adjust the different biosynthetic pathways providing substrates with the massive and variable demands of different biosynthetic reactions of cell wall polymers. Although a few genes have been reported as differentially expressed in differentiating compression wood compared to normal or opposite wood, the expression of a larger set of genes is expected to change due the broad range of features that distinguish this reaction wood. By combining the construction of different cDNA libraries with microarray analyses, using samples from different Pinus pinaster provenances collected in different years and geographic locations, we have identified a total of 496 genes that change their expression during differentiation of compression wood (331 up-regulated and 165 down-regulated compared to opposite wood). Consistent with the well-known structural and chemical characteristics of compression wood, a large number of genes involved in the biosynthesis of cell wall components were shown to be up-regulated during compression wood differentiation, including genes involved in synthesis of cellulose, hemicellulose, lignin and lignans. In particular, further analysis of a set of these genes involved in providing S-adenosylmethionine, ammonium recycling, lignin and lignans biosynthesis showed parallel expression profiles to levels of lignin accumulation in cells undergoing xylogenesis in vivo and in vitro. The comparative transcriptomic analysis of compression and opposite wood formation in this work have revealed a broad spectrum of coordinated transcriptional modulation of biosynthetic reactions for different cell wall polymers associated to within-tree variations in softwood structure and composition. In particular, it suggest the occurrence of a mechanism that modulates at transcriptional level genes encoding enzymes involved in S-adenosylmethionine synthesis and ammonium assimilation with coniferyl alcohol demand for lignin and lignan synthesis, as a key metabolic requirement in cells undergoing lignification.
2012-05-06 | GSE37736 | GEO