Differential synaptic signaling responses in human cortical organoids after photon and proton irradiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE311001 | GEO | 2026/02/03
REPOSITORIES: GEO
Similar Datasets
Project description:The specific impact of different radiation types, such as photons and protons, and their effects on normal stem cell activity and tissue regeneration are unknown. In this study, we used a scRNA-seq approach to characterize our mouse salivary gland organoid model and to assess the effects of photon and proton irradiation on salivry gland stem/progenitor cells.
2025-11-18 | GSE253048 | GEO
Project description:The specific impact of different radiation types, such as photons and protons, and their effects on normal stem cell activity and tissue regeneration are unknown. In this study, we used bulk RNA sequencing to identify differences between photon and proton irradiation using 3 different doses at an early and late timepoint.
2025-11-18 | GSE253034 | GEO
Project description:The specific impact of different radiation types, such as photons and protons, and their effects on normal stem cell activity and tissue regeneration are unknown. In this study, we used a scRNA-seq approach to characterize our mouse salivary gland organoid model at day 7 and 11 and assess the effects of photon and proton irradiation on salivary gland stem/progenitor cells at day 7.
2025-09-23 | GSE272759 | GEO
Project description:We performed comparative RNA sequencing of the early (4 hrs) dose response (0.5 – 200 cGy whole body dose, 10 dose levels) of the mouse aorta to proton and gamma radiation. Total-body proton radiation of conscious animals was performed using a proton beam produced by a cyclotron system, while total-body gamma radiation of animals was performed using a Caesium-137 gamma source. A trend analysis identified genes that showed a dose response, using data permutation to estimate a false discovery rate (q-value) for each gene. We identified 29 and 194 genes (q-value ≤ 0.1) that were upregulated with increasing doses of proton and gamma radiation, respectively. No genes were down-regulated. While fewer genes were dose-responsive to proton radiation, the magnitude of the effect was greater than with gamma radiation. These highly responsive genes were enriched for pathways involved in the response to DNA damage, apoptosis, cellular stress and inflammation (p < 0.01). Gamma radiation responsive genes included the same pathways, but extended to genes in vasculature specific pathways. Genes responsive to both radiation types (19 genes at q-value ≤ 0.1) showed almost perfectly superimposable dose-response relationships. We observed the same superimposable dose response relationship of gamma and proton radiations in a subset of genes validated by quantitative PCR not only in the aorta but also in liver, lung, heart and kidney. Despite a relative similar relative biological effectiveness of protons and gamma photons and the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response. It seems plausible that these genomic differences translate into differences in the biological processes leading to cardiovascular pathologies.
2019-01-25 | GSE105266 | GEO
Project description:The growing number of particle treatment facilities worldwide and patients treated with particles instead of X-rays marks the upcoming rearrangement of modern radiotherapy. Especially for tumors being difficult to access and for tumors that are resistant to conventional X-ray treatment particle radiotherapy is a beneficial technology. At the Heidelberg Ion Beam Therapy Center (HIT) patients are treated with this technology since 2009 as it offers clear benefits. Contrary to X-rays, which show an exponential dose decrease (after reaching electron equilibrium) with increasing tissue depth, charged particles deposit most of their energy to a small region within the tissue with a sharp dose fall-off after the so-called Bragg peak. This precise dose localization enables further dose escalation within the tumor while sparing healthy tissue. Besides physical advantages, particle radiotherapy offers additional biological advantages. In radiobiology, the term relative-biological effectiveness (RBE) is defined as the ratio of X-rays dose to an alternative irradiation modality dose which produce the same biological effect (e.g. survival or number of DSBs). While protons have a relative biological effectiveness (RBE) comparable to X-rays, carbon ions are more effective in inducing DNA damage(1, 2) and are therefore especially useful for radioresistant tumors. This is due to the fact, that carbon ions induce clustered and direct DNA damage, which is considered to be less dependent on cell cycle stage, oxygen level, genetic background and hinders DNA repair mechanisms(3–6). Nevertheless, their exact mode of action and cellular mechanisms are largely unknown. We show the first comprehensive proteomic and phosphoproteomic study elucidating the cellular response to treatment with protons, carbon ions and X-rays. We found that 2h after treatment with these radiations negligible regulation occurred at protein expression level. But 181 phosphorylation sites were deregulated by ionizing radiation contributing mainly to DNA damage response functionalities. Interestingly we found 55 phosphorylation sites being differentially regulated between the radiations. Here, we observed protons and carbon ions producing equal cellular response whereas X-rays show altered regulation for certain phosphorylation sites. A subset of 28 phosphorylation sites being involved in the DNA damage response or differentially regulated between the ionizing radiations was selected for result confirmation.
2017-03-20 | PXD004817 | Pride
Project description:Differential synaptic signaling responses in human cortical organoids after photon and proton irradiation
| PRJNA1368307 | ENA
Project description:Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to “hallmark” processes impacting tumor development, in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally, protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74, and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation, operative through host age, that would indicate a modulation of host’s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression, carcinogenesis, and genetic perturbation by old age. For genome-wide expression profiling of tumor tissue, Mouse WG-6 BeadArray chips (Illumina, San Diego, CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion, Austin, TX) and labeled from all replicate biological samples for each condition. For spleen replicates, 9 spleen samples from adolescent with 0Gy , 10 from adolescent with 0.5Gyx3 protons, 9 from old from old with 0Gy, and 10 from old mice with 0.5Gyx3 protons, were used. All replicate samples were run individually. Total RNA was isolated and purified using TRIzol (Invitrogen) and quantified using an Agilent Bioanalyzer. Samples were deemed suitable for amplification and hybridization if they had 28s/18s = 2:1, RIN >7. Total RNA of 500ng per sample was amplified using AmbionTotalPrep, and 1.5ug of the product was loaded onto the chips. Following hybridization at 55C, the chips were washed and then scanned using the Illumina iScan System. The data was checked with GenomeStudio (Illumina) for quality control. Data were corrected through COMBAT correction, quantile normalized, collapsed to genes from probes, then imported into MultiExperiment Viewer, MeV for analysis. Statistically significant genes were determined by applying a one-way ANOVA with an adjusted Bonferroni correction and false discovery rate (FDR) < 0.001 that resulted in a list of significant genes.
2015-06-22 | E-GEOD-67243 | biostudies-arrayexpress
Project description:Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to “hallmark” processes impacting tumor development, in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally, protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74, and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation, operative through host age, that would indicate a modulation of host’s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression, carcinogenesis, and genetic perturbation by old age.
2015-06-22 | GSE67243 | GEO
Project description:Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that, in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition, age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV), with increased inhibition evident in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support, which can be further inhibited by proton irradiation.
2014-01-01 | GSE45609 | GEO
Project description:Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that, in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition, age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV), with increased inhibition evident in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support, which can be further inhibited by proton irradiation. For genome-wide expression profiling of tumor tissue, Mouse WG-6 BeadArray chips (Illumina, San Diego, CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion, Austin, TX) and labeled from all replicate biological samples for each condition. For tumor replicates, thirty tumor samples from adolescent and thirty tumor samples from old mice, for a total of 60 tumor samples, were used. All replicate samples were run individually. For each age group, ten tumor samples had received proton irradiation while twenty tumor samples were from unirradiated mice (as described above). Total RNA was isolated and purified using TRIzol (Invitrogen) and quantified using an Agilent Bioanalyzer. Samples were deemed suitable for amplification and hybridization if they had 28s/18s = 2:1, RIN >7. Total RNA of 500ng per sample was amplified using AmbionTotalPrep, and 1.5ug of the product was loaded onto the chips. Following hybridization at 55C, the chips were washed and then scanned using the Illumina iScan System. The data was checked with GenomeStudio (Illumina) for quality control. In GenomeStudio, data was background subtracted and rank invariant normalization was applied. Data was imported into MultiExperiment Viewer, MeV, for statistical analysis. The statistically significant genes were determined using MeV by applying a one-way ANOVA analysis with standard Bonferroni correction with a FDR <0.05 that resulted in a list of significant genes. Average gene expression signals <10 were filtered out due to signal being
2014-01-01 | E-GEOD-45609 | biostudies-arrayexpress