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.
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
Project description:Meniscus injuries are highly prevalent and are linked to the development of post-traumatic osteoarthritis (PTOA). The inflammatory cytokine IL-1 is elevated in synovial fluid following knee injuries, causes degradation of meniscus tissue, and inhibits meniscus repair. Dynamic mechanical compression of meniscus tissue has been shown to improve integrative repair in the presence of IL-1; however, there remains a dearth of knowledge on global effects of loading on meniscus cell phenotype and transcriptomic profiles. In this study, we performed mRNA-Seq on meniscus tissue explants from inner and outer zone regions of porcine menisci subjected to dynamic compression in the presence and absence of IL-1 to identify cellular responses to mechanical load, identify differences in response to load based on zonal characteristics, and identify IL-1 induced inflammatory responses modulated by load.
Project description:Mechanosensing is required for the senses of touch and hearing, and impacts on cellular processes such as cell differentiation, migration, invasion and tissue homeostasis. Mechanical inputs give rise to p38- and JNK-signaling, which mediates adaptive physiological responses in various tissues. In muscle, fiber contraction-induced p38 and JNK signaling ensures adaptation to exercise, muscle repair and hypertrophy. However, the mechanism by which muscle fibers sense mechanical load to activate this signaling, as well as the physiological roles of mechanical stress sensing more broadly, have remained elusive. Here, we show that the upstream MAP3K ZAK is a sensor of cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAK’s ability to recognize stress fibers in cells and the corresponding Z-discs in muscle fibers, when under tension. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general sense mechanical compressive load, and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.
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.
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.
Project description:Mechanical force is a crucial external stimulus that plays a significant role in regulating bone structure and remodeling. Excessive loading of the bone and joint can lead to increased catabolism, chondrocyte necrosis, apoptosis and damage to the collagen network of bone(3–5). Osteoarthritis (OA), a degenerative osteoarticular disease, is associated with abnormal mechanical force stimulation, which can occur in various joints such as knee, temporomandibular joint [TMJ], shoulder and hip(6). Conversely, the absence of mechanical loading, such as prolonged bed rest or exposure to a microgravity environment in space, can result in a rapid decrease in bone mass and strength. Understanding how mechanical stimuli regulate bone homeostasis is crucial for exploring therapeutic strategies for bone metabolic diseases.Mesechymal stem cells (MSCs) act as the external force sensoring and compression-bearing elements.What we want to explore is how mechanical stimulation affects the genome changes of mesenchymal stem cells.