BULK RNA SEQ OF HUVEC - NON-TARGETING AND SUN1, STATIC AND FLOW
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213099 | GEO | 2023/03/13
REPOSITORIES: GEO
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Project description:The inner nuclear envelope (NE) proteins interact with the nuclear lamina and participate in the architectural compartmentalization of chromosomes. The association of NE proteins with DNA contributes to the spatial rearrangement of chromosomes and their gene expression. Sun1 is an inner nuclear membrane (INM) protein that locates to telomeres and anchors chromosome movement in the prophase of meiosis. Here, we have created Sun1-/- mice and found that these mice are born and grow normally but are reproductively infertile. Detailed molecular analyses showed that Sun1-/- P14 testes are repressed for the expression of reproductive genes and have no detectable piRNA. These findings raise a heretofore unrecognized role of Sun1 in the selective gene expression of coding and non-coding RNAs needed for gemetogenesis. Total RNA was isolated from E14.5 mouse embryonic fibroblasts (MEFs) and and day 9 and 14 mouse whole testes. cDNA samples from paired (same parents) wt (Cy3-labled) and Sun1-/- (Cy5-labled) mice were mixed and hybridized.
2009-03-11 | E-GEOD-12867 | biostudies-arrayexpress
Project description:Mesenchyal Stem Cells (MSCs) differentiation into multiple lineages, such as osteocytes and adipocytes, has been shown to be regulated by mechanical signals. The Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex has been shown to be required for mechanical signal transduction, regulation of MSCs differentiation, and nuclear integrity. The LINC complex is made of Nesprins and Sun proteins. Nesprin proteins associate with the cytoskeleton on the outer nuclear membrane and Sun proteins are bound to the inner nuclear membrane where they bind to inner nuclear proteins and chromatin. We investigated the role of the Sun1/2 in regulating the inner nuclear functions of chromatin organization and adipogenic differentiation independently of the LINC complex function. We show that depletion of Sun1/2 increased nuclear area and perimeter, and decreased circularity. Expression of a dominant-negative KASH (dnKASH) domain targeting the SUN domain on Sun proteins inhibiting Nesprin-SUN association resulting a loss of Nesprin localization to the nuclear envelope decreased nuclear area and circularity. Adipogenesis was inhibited during Sun1/2 depletion while dnKASH expression accelerated adipgoenesis. RNA-seq data showed decreased adipogensis and increased immune response during Sun1/2 depletion. dnKASH responded oppositely with increased adipogenic gene expression and decreased immune response. We also observed increased H3K9me3 levels, increased H3K9me3 foci count, and enrichment on Adipoq during Sun1/2 depletion. No increase of H3K9me3 levels, foci count, or increased H3K9me3 enrichment on Adipoq was found during dnKASH expression. We conclude that physically decoupling of the LINC complex via dnKASH accelerates adipogenesis and that Sun1/2 regulates chromatin organization and adipogenesis independently of the LINC complex function.
2022-07-13 | GSE193505 | GEO
Project description:The inner nuclear envelope (NE) proteins interact with the nuclear lamina and participate in the architectural compartmentalization of chromosomes. The association of NE proteins with DNA contributes to the spatial rearrangement of chromosomes and their gene expression. Sun1 is an inner nuclear membrane (INM) protein that locates to telomeres and anchors chromosome movement in the prophase of meiosis. Here, we have created Sun1-/- mice and found that these mice are born and grow normally but are reproductively infertile. Detailed molecular analyses showed that Sun1-/- P14 testes are repressed for the expression of reproductive genes and have no detectable piRNA. These findings raise a heretofore unrecognized role of Sun1 in the selective gene expression of coding and non-coding RNAs needed for gemetogenesis.
2009-03-11 | GSE12867 | GEO
Project description:Alteration of the size and stiffness of the nucleus triggered by environmental cues are thought to be important for eukaryotic cell fate and function. Here we identify the nuclear envelope proteins SUN1/2 as mechano-regulators of the nucleus during M1 polarization of the macrophage. Specifically, we show that LPS treatment decreases the protein levels of SUN1/2 in a CK2-bTrCP-dependent manner to shrink and soften the nucleus, therefore altering the chromatin accessibility for M1-associated gene expression.
2023-09-28 | GSE243684 | GEO
Project description:Chromosomes pair and synapse with their homologous partners to segregate correctly at meiosis I. Association of telomeres with the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex enables telomere-led chromosome movements and telomere bouquet formation, facilitating precise pairwise alignment of homologs. Here, we identify a direct interaction between SUN1 and Speedy A (SPDYA) and determine the crystal structure of human SUN1-SPDYA-CDK2 ternary complex. Analysis of meiosis prophase I process in SPDYA-binding-deficient SUN1 mutant mice reveals that the SUN1-SPDYA interaction is required for the telomere-LINC complex connection and the assembly of a ring-shaped telomere supramolecular architecture at the nuclear envelope, which is critical for efficient homologous pairing and synapsis. Overall, our results provide structural insights into meiotic telomere structure that is essential for meiotic prophase progression.
2021-04-08 | GSE155142 | GEO
Project description:T cell infiltration is essential for immune checkpoint inhibitors to be effective in treating solid cancers. Through a bioinformatic pipeline, we identified a target gene SUN1 that might relate to modulating immune cell infiltration and immune response. Thus, we generated one Sun1_knockout CT26 cell line (Sun1_KO) and two control CT26 cell lines (Sun1_Control) using CRISPR-Cas9. By performing RNA-seq on cultured cells, tumors grown in syngeneic model, and purified tumor cells from tumors grown in syngeneic model, we set out to understand how mouse Sun1 can affect immune-related pathways and immune cell infiltration and anti-PD1 efficacy in BALB/c mice.
2024-03-29 | GSE250602 | GEO
Project description:SUN1/2 are located on the inner nuclear envelope membrane, which comprise an N-terminal nucleoplasmic domain, a transmembrane segment and a C-terminal SUN domain. The nucleoplasmic domain of SUN1/2 interacts with lamina and/or chromatin binding proteins, while the SUN domain protrudes into the lumen of the nuclear envelope to interact with KASH proteins in a trimeric fashion. Defects in SUN proteins have been linked to human diseases including laminopathies, ataxia, progeria, lissencephaly, and cancer. To explore the role of SUN1/2 during macrophage activation, we explore microarray analysis of THP-1-derived macrophages after stable transfection of siVGLL4 for 48 h.
2019-09-01 | GSE85022 | GEO
Project description:T cell infiltration is essential for immune checkpoint inhibitors to be effective in treating solid cancers. Through a bioinformatic pipeline, we identified a target gene SUN1 that might relate to modulating immune cell infiltration and immune response. Thus, we generated one Sun1_knockout CT26 cell line (Sun1_KO) using CRISPR-Cas9. By performing multiome single nuclei sequencing using tumors grown in syngeneic model, we set out to understand how mouse Sun1 can affect the regulatory network in tumor cells in vivo.
2024-03-29 | GSE262237 | GEO
Project description:Depletion of Sun1/2 Induces Heterochromatin Accrual in MSCs
| PRJNA796421 | ENA
Project description:Vascularization represents an important issue in bone development, fracture healing and engineering of artificial bone tissue. In the context of bone tissue engineering, it was shown that coimplantation of human primary umbilical vein endothelial cells (HUVECs) and human osteoblasts (hOBs) results in the formation of functional blood vessels and enhanced bone regeneration. Implanted endothelial cells do not only contribute to blood vessel formation, but also support proliferation, cell survival and osteogenic differentiation of coimplanted hOBs. These effects are partially mediated by direct heterotypic cell contacts. In a previous report we could show that cocultivated hOBs strongly increase the expression of genes involved in extracellular matrix (ECM) formation in HUVECs, suggesting that ECM may be involved in the intercellular communication between hOBs and HUVECs. The present study aimed at investigating whether comparable changes occur in hOBs. We therefore performed a microarray analysis of hOBs cultivated in direct contact with HUVECs, revealing 1121 differentially expressed genes. The differentially expressed genes could be assigned to the functional clusters ECM, proliferation, apoptosis and osteogenic differentiation. In summary, our data demonstrate that HUVECs provoke complex changes in gene expression patterns in cocultivated hOBs and that ECM plays and important role in this interaction.
2015-12-17 | E-MTAB-4152 | biostudies-arrayexpress