Next-generation sequencing facilitates quantitative analysis of rat BMSCs in fast, medium or slow stress relaxation SA hydrogel
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE186726 | GEO | 2021/11/01
REPOSITORIES: GEO
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Project description:Next-generation sequencing facilitates quantitative analysis of rat BMSCs in fast, medium or slow stress relaxation SA hydrogel
| PRJNA775649 | ENA
Project description:Type 2 diabetes mellitus (T2DM) is a major risk factor for hepatocellular carcinoma (HCC). Changes in extracellular matrix (ECM) mechanics contribute to cancer development, and increased stiffness is known to promote HCC progression in cirrhotic conditions. T2DM is characterized by an accumulation of advanced glycation end products (AGEs) in the ECM; however, how this affects HCC in non-cirrhotic conditions is unclear. Here, we find that in patients and animal models AGEs promote changes in collagen architecture and enhance ECM viscoelasticity, with greater viscous dissipation and faster stress relaxation, but not changes in stiffness. High AGEs and viscoelasticity combined with oncogenic b-catenin signaling promote HCC induction, while inhibiting AGEs production, reconstituting the clearance receptor AGER1, or breaking AGE-mediated collagen crosslinks reduce viscoelasticity and HCC growth. Matrix analysis and computational modeling demonstrate that lower interconnectivity of AGEs-bundled collagen matrix, marked by shorter fiber length and greater heterogeneity, enhance viscoelasticity. Mechanistically, animal studies and 3D cell cultures show that enhanced viscoelasticity promotes HCC cell proliferation and invasion through an integrin β1–Tensin 1–YAP mechanotransduction pathway. These results reveal for the first time that AGEs-mediated structural changes enhance ECM viscoelasticity, and that viscoelasticity can drive cancer progression in vivo, independent of stiffness.
2023-10-14 | GSE245016 | GEO
Project description:The efficacy of adoptive T cell therapy is highly dependent on the generation of T cell populations that are able to both provide immediate effector function and long-term protective immunity. Inspired by the emerging consensus that T cell phenotype and function are inherently linked to their tissue localization, we present an approach to generate functionally distinct T cell populations via the physical properties of their surrounding matrix. A collagen type I based extracellular matrix (ECM) was engineered to allow for independent tuning of matrix stiffness and viscoelasticity, two features that characterize the mechanical properties of tissues. To investigate how ECM viscoelasticity drives changes in the transcriptional landscape of T cells, scRNA-seq of CD8+ T cells cultured in fast relaxing and slow relaxing collagen matrices was performed
2023-05-02 | GSE230628 | GEO
Project description:Human induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biochemical and biomechanical signaling cues imparted by the neural extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels crosslinked with either static or dynamic covalent bonds that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in the expression of neural maturation genes. Taken together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.
2023-10-31 | GSE236334 | GEO
Project description:Purpose: To identify genes and the molecular pathways involved in the MSCs response to extracellular matrix stiffness, we performed RNA-sequencing of MSCs which cultured in soft (2 kPa) and stiff (18 kPa) SA hydrogels. Methods: mRNA profiles of MSCs cultured in soft (2 kPa) and stiff (18 kPa) SA hydrogel for 48 h were generated by deep sequencing, in quadruplicate, using Illumina HiSeq 2000. Results: Using an optimized data analysis workflow, we identified 33950 transcripts in MSCs with BWA workflow. Conclusions: Our results present the detailed analysis of MSCs transcriptomes cultured in soft (2 kPa) and stiff (18 kPa) matrix, and found that matrix stiffness dominated multiple mRNA pathways in MSCs.
2021-08-06 | GSE181512 | GEO
Project description:We analyze the transcriptomic response of the phytopathogenic enterobacterium Dickeya dadantii to a DNA supercoiling relaxation shock using the gyrase inhibitor novobiocin. The shock was applied to Dickeya cells grown in minimal medium supplemented with sucrose, in exponential or transition to stationary phase, and in minimal medium with sucrose + PGA (a pectin derivative) in transition to stationary phase.
2019-04-16 | E-MTAB-7650 | biostudies-arrayexpress
Project description:We analyze the transcriptomic response of the phytopathogenic enterobacterium Dickeya dadantii ihfA mutant to a DNA supercoiling relaxation shock using the gyrase inhibitor novobiocin. The shock was applied to Dickeya cells grown in minimal medium supplemented with sucrose, in exponential or transition to stationary phase, and in minimal medium with sucrose + PGA (a pectin derivative) in transition to stationary phase.
2021-02-10 | E-MTAB-9025 | biostudies-arrayexpress
Project description:Thousands of long intergenic noncoding RNAs (lincRNAs) are encoded by the mammalian genome, which were reported to have multiple biological functions as transcriptional activators acting in cis 1 or trans 2, transcriptional repressors 3,4 or miRNAs decoys 5,6. However, the function of most lincRNAs has not yet been identified in vivo. Here, we demonstrate a role for linc-MYH, a novel long intergenic noncoding RNA, in adult fast-type myofibre specialization. Skeletal myofibre fast and slow phenotypes are established through differential expression of numerous fibre-specific genes7. We show linc-MYH and the fast MYH genes share a common enhancer located in the fast MYH genes locus and regulated by the Six1 homeoproteins. Muscle-specific Six1 mutant mice show increased expression of slow-type genes, and downregulation of linc-MYH and fast-type genes. linc-MYH function revealed by in vivo knockdown and wide transcriptomic analysis, is in fine to prevent expression of genes ensuring slow muscle contractile properties, and to increase fast-type muscle gene expression in fast-type myofibres. Thus, formation of efficient fast sarcomeric units and appropriate Ca++ cycling and excitation/contraction/relaxation coupling in fast- myofibres is achieved through the coordiante control of fast MYHs and linc-MYH expression by a Six bound enhancer.
2014-04-27 | GSE46151 | GEO
Project description:We have analyzed the transcriptomes of Dickeya dadantii wild type, fis and hns strains in condition of DNA relaxation induced by novobiocin, a DNA gyrase inhibitor. For DNA relaxation novobiocin was added for 15 min to 100µg/ml final concentration to exponentially growing wild type, hns and fis strains (OD600= 0.2) grown in M63 medium supplemented by sucrose 0.2% (w/v). At this concentration, novobiocin has no impact on D. dadantii growth The micro-arrays used in this study were custom designed and produced by Roche NimbleGen, Inc. (Madison, WI) based on the annotated sequence of D. dadantii, available at Genbank accession number n° CP002038, which comprises 4597 CDS. The 4plex expression micro-arrays consist of 60-mer oligonucleotides, triplicated in three blocks on the array (5 oligonucleotides per CDS). For micro-array analyses, cDNA was synthesized, labeled and hybridized by Roche NimbleGen Inc.
2015-04-16 | E-MTAB-2597 | biostudies-arrayexpress
Project description:Skeletal muscle weakness has been associated with different pathological conditions, including sarcopenia and muscular dystrophy, and is accompanied by altered mTOR signaling. Here we wanted to better elucidate the functional role of mTOR on muscle contractility. Most loss of function studies for mTOR signaling have used the drug rapamycin to inhibit some of the signaling downstream of mTOR. However, as rapamycin does not completely inhibit all mTOR signaling, we generated a double k.o. for mTOR and for the scaffold protein of mTORC1, Raptor, in skeletal muscle. We found that dk.o. mice results in a more severe phenotype compared to Raptor or mTOR deletion alone. Indeed, they display muscle weakness, increased fiber denervation, and a slower muscle relaxation following tetanic stimulation. This is accompanied by a shift towards slow-twitch fibers and changes in the expression levels of calcium-related genes, like Serca1 and Casq1. Indeed, dk.o. mice show a decrease in calcium decay kinetics after tetanus in vivo, suggestive of a reduced calcium reuptake. In addition, RNA sequencing analysis revealed that many downregulated genes are linked to sarcomere organization, like Tcap and Fhod3. These results suggest a key role for mTOR signaling in maintaining a proper fiber relaxation in skeletal muscle.
2022-10-19 | GSE215314 | GEO