Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1309696 | ENA |
REPOSITORIES: ENA
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Project description:Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface. Using a novel Wnt signaling reporter system, we have identified a Wnt-responsive alveolar epithelial sublineage arising during alveologenesis called the axin2+ alveolar type 2 cell or AT2Aaxin2. The number of AT2Aaxin2 sublineage cells increases substantially during late lung development, revealing a wave of Wnt signaling during alveologenesis. Transcriptome analysis, in vivo clonal analysis, and ex vivo lung organoid assays reveal that AT2sAaxin2s promote enhanced AT2 cellalveolar growth during generation of the alveolus compared to the overall AT2 population. Activating Wnt signaling in the AT2 lineage results in expansion of the AT2axin2 sublineageAT2s whereas inhibition of Wnt signaling inhibits AT2 cell development and shunts alveolar epithelial development towards the AT1 cell lineage. These findings reveal a novel epithelial sublineage that coordinates Wnt-dependent alveolar growthAT2 expansion required for lung alveologenesis
2016-11-30 | GSE82154 | GEO
Project description:In all primary cells analyzed to date, aneuploidy is associated with poor proliferation. Yet, how abnormal karyotypes affect cancer – a disease characterized by both aneuploidy and heightened proliferative capacity – is largely unknown. Here, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally-unstable cancer cell lines, but are not common to all aneuploid cancers. Moreover, chromosomally-unstable cancer lines display increased glycolytic and TCA-cycle flux, as is also observed in primary aneuploid cells. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells is a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlates with high mitotic activity and poor prognosis. I speculate that there are two types of aneuploidy in cancer: clonal aneuploidy, which is selected during tumor evolution and is associated with robust growth, and sub-clonal aneuploidy, which is caused by chromosomal instability (CIN) and more closely resembles the stressed state of primary aneuploid cells. Nonetheless, CIN is not benign: a subset of genes upregulated in high-CIN cancers predict aggressive disease in human patients in a proliferation-independent manner. The mRNAs from 3 different mouse embryo fibroblast (MEF) lines that are chromosomally stable were compared with mRNAs from 3 different MEF lines that were chromosomally unstable due to mutations in either BUBR1 or CDC20
2013-10-01 | E-GEOD-49894 | biostudies-arrayexpress
Project description:A cross-sectional study was conducted between 2012 and 2023 to collect breast tumor and tumor-adjacent normal tissue (N=48 tumor, 41 tumor-adjacent normal) from women with breast cancer. Participants were recruited through the University of Maryland Medical Center and other hospital sites within the area of Baltimore, Maryland. RNA-sequencing and whole exome sequencing was performed on these fresh-frozen tissues. Genomic DNA was extracted from frozen breast tumors and adjacent normal tissue using the Qiagen DNeasy Blood & Tissue kit and checked for quality using the Agilent Genomic DNA Screen tape assay. WES was performed by the service provider Psomagen and data processed as in Tang, et al, 2023.
2025-02-14 | GSE267505 | GEO
Project description:The present study investigated whether maternal periodontal disease modifies the microRNA expression profile in adult offspring. *************************************************************** This study was supported by the São Paulo Research Foundation (FAPESP) [grant #2019/04183-9; #2022/08872-6; #2023/03786-7; #2023/12488-0; #2023/01400-4] and CNPq [grant 151151/2023-7], São Paulo, SP, Brazil. The grants #2019/04183-9; #2023/12488-0; #2023/01400-4 and 151151/2023-7 were awarded to the author Maria Sara de Lima Coutinho Mattera. The grant #2022/08872-6 was awarded to Heloisa Macedo Sampaio. The grant #2023/03786-7 was awarded to Gabriele Fernandes Baliero. ***************************************************************
2024-12-28 | GSE281235 | GEO
Project description:Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by clonal expansion of myeloid cells, notably megakaryocytes (MKs), and aberrant cytokine production leading to bone marrow (BM) fibrosis and insufficiency. Current treatment options are limited. TGF-b1, a profibrotic and immunosuppressive cytokine, is involved in PMF pathogenesis. While all cell types secrete inactive, latent TGF-b1, only a few activate the cytokine via cell type-specific mechanisms. The cellular source of the active TGF-b1 implicated in PMF is not known. Transmembrane protein GARP binds and activates latent TGF-b1 on the surface of regulatory T lymphocytes (Tregs) and MKs or platelets. Here, we found increased expression of GARP in BM and spleen of mice undergoing PMF and tested the therapeutic potential of a monoclonal antibody that blocks TGF-b1 activation by GARP-expressing cells. GARP:TGF-b1 blockade reduced not only fibrosis, but also clonal expansion of transformed cells. Using mice carrying a genetic deletion of Garp in either Tregs or MKs, we found that the therapeutic effects of GARP:TGF-b1 blockade in PMF imply targeting GARP on Tregs. These therapeutic effects, accompanied by increased IFN-g signals in the spleen, were lost upon CD8 T cell depletion. Our results suggest that selective blockade of TGF-b1 activation by GARP-expressing Tregs increase a CD8 T cell-mediated immune reaction that limits transformed cell expansion, providing a novel approach that could be tested to treat patients with myeloproliferative neoplasms.
2022-10-27 | GSE216221 | GEO
Project description:In all primary cells analyzed to date, aneuploidy is associated with poor proliferation. Yet, how abnormal karyotypes affect cancer – a disease characterized by both aneuploidy and heightened proliferative capacity – is largely unknown. Here, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally-unstable cancer cell lines, but are not common to all aneuploid cancers. Moreover, chromosomally-unstable cancer lines display increased glycolytic and TCA-cycle flux, as is also observed in primary aneuploid cells. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells is a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlates with high mitotic activity and poor prognosis. I speculate that there are two types of aneuploidy in cancer: clonal aneuploidy, which is selected during tumor evolution and is associated with robust growth, and sub-clonal aneuploidy, which is caused by chromosomal instability (CIN) and more closely resembles the stressed state of primary aneuploid cells. Nonetheless, CIN is not benign: a subset of genes upregulated in high-CIN cancers predict aggressive disease in human patients in a proliferation-independent manner.
2013-10-01 | GSE49894 | GEO
Project description:Immune checkpoint blockade (ICB) therapy is a standard treatment option for many malignancies, but it is only effective in a subset of patients. Combination strategies to overcome resistance are promising areas of investigation. Targeting glucocorticoidinduced TNFR-related (GITR) protein with agonist antibodies has shown efficacy in preclinical models, but GITR engagement does not control growth of advanced poorly immunogenic murine tumors such as B16 melanoma and has not yielded benefit in clinical trials. The alkylating agent cyclophosphamide (CTX) preferentially depletes regulatory T cells (Tregs) and expands tumor-specific effector T cells (Teffs) via homeostatic proliferation. Additionally, CTX directly induces tumor cell death, thereby releasing antigen to prime Teffs in a lymphopenic environment where there are fewer Tregs. GITR agonism has a net inhibitory effect on Tregs and yet activates Teff. We therefore hypothesized that CTX treatment prior to GITR agonism would promote potent anti-tumor immunity. Here we show that the combination of CTX and GITR agonism robustly controls tumor growth in several clinically relevant mouse models. Mechanistically, we show that the combination therapy causes tumor cell death, clonal expansion of highly active and terminally differentiated CD8+ T cells, and depletion of regulatory T cells by AICD. Control of tumor growth was also associated with the presence of an expanded population of highly activated tumor-infiltrating oligoclonal CD8+ T cells that lead to a global contracted TCR repertoire. Our studies show that the combination of CTX and GITR agonism is a rational chemo-immunotherapeutic approach that warrants further clinical investigation.
2021-11-18 | GSE182292 | GEO
Project description:To gain further molecular insight into the observed astrocyte functions, we performed RNA-sequencing (RNA-seq) analysis of the differentiated Ctx-NPCs (control), Ctx-astrocytes and VM-astrocytes used in the co-culture and CM experiments. The genes that are differentially expressed (DEGs) in Ctx-astrocytes compared to differentiated Ctx-NPCs (FPKM>1, log2>1) significantly overlapped with DEGs in VM-astrocytes compared to differentiated Ctx-NPCs
2020-10-25 | GSE106216 | GEO
Project description:Transcriptional profiling comparing Escherichia coli simultaneously exposed to tellurite and CTX with untreated control cells; Tellurite with control; CTX with control Three-condition experiment, antibacterial (tellurite; CTX or tellurite/CTX) vs. Untreated control cells. Biological replicates: 3 control, 3 toxicants exposed cells, independently grown and harvested. One replicate per array.
2013-09-01 | E-GEOD-39696 | biostudies-arrayexpress
Project description:In present study, it was found that the co-culture of Wickerhamomyces anomalus Y-5 and L. plantarum RX-8 could enhance bacteriocin production. To analyze the interaction between W. anomalus Y-5 and L. plantarum RX-8, a quantitative proteomic approach was used to analyze and compare the proteome in L. plantarum RX-8 and W. anomalus Y-5 under mono-culture and co-culture. In total, 339 differently expressed proteins (DEPs) were screened in comparison of L. plantarum RX-8 under mono-culture and co-culture, 645 proteins of W. anomalus Y-5 changed in mono-culture and co-culture. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that DEPs participated in various metabolic pathways such as PTS system, glycolysis, galactose metabolism, glutamate, aspartate, arginine and cysteine metabolism etc. These pathways were related to inducing mechanism on improving bacteriocin production by co-culture. Quantitative proteomic analysis-based strategies can therefore provide further evidence for new regulated targets to improve the production of bacteriocins.
2022-12-04 | PXD038315 | Pride