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Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts

ABSTRACT: Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts

PROVIDER: PRJNA449373 | ENA |

REPOSITORIES: ENA

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Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 1]

Project description:Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 1]

| PRJNA449075 | ENA

Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 2]

Project description:Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 2]

| PRJNA449369 | ENA

Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 2]

Project description:To study delayed genetic and epigenetic radiation effects, which may trigger radiation-induced carcinogenesis, we have established single-cell clones from irradiated and non-irradiated primary human fibroblasts. Stable clones were endowed with the same karyotype in all analyzed metaphases after 20 population doublings (PDs), whereas unstable clones displayed mosaics of normal and abnormal karyotypes. To account for differences in radiation sensitivity, all experiments were performed with two different embryonic fibroblast strains. After a single dose of 2 Gray more than half of the irradiated clones exhibited radiation-induced genomic instability (RIGI). Methylation arrays identified several hundred differentially methylated genes and nine enriched pathways associated with in vitro ageing. Methylation changes in 259 genes and the MAP kinase signaling pathway were associated with delayed radiation effects (after 20 PDs). Collectively, our results suggest that both genetic and epigenetic changes occur in the progeny of exposed cells that were not damaged directly by irradiation, likely contributing to radiation-induced carcinogenesis.

2018-04-10 | GSE112873 | GEO

Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts [strain 1]

2018-04-07 | GSE112812 | GEO

Genetic and epigenetic changes in clonal descendants of irradiated human fibroblasts

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-04-10 | GSE112877 | GEO

Isolation of repaired chromatin of UVC-irradiated human skin fibroblasts

Project description:To further study and understand the DNA damage responses, we developed aniFOUND, a new method for capturing under native conditions the repaired DNA and the proteins associated with it after UVC irradiation. hTert-immortalised human skin fibroblasts were irradiated with 20 J/m2 UVC and the nascent DNA that resulted from the Unscheduled DNA Synthesis was specifically labeled with nucleotide analogues (EdU). This newly repaired/synthesized DNA together with the bound proteins were pulled-down with streptavidin beads. For negative controls we used both irradiated, but non-labelled samples (+UV/-EdU) and labelled, but not irradiated cells (-UV/+EdU). The pulldowns were eluted from the beads by boiling in 0.1 % SDS.

2021-03-10 | PXD012997 | Pride

Gene expression of chronically UVA1-irradiated human dermal diploid fibroblasts

Project description:Gene expression of chronically UVA1-irradiated human dermal diploid fibroblasts

2019-01-23 | GSE125429 | GEO

Gene expression of human corneal epithelial cells grown with irradiated human fibroblasts or irradiated mouse 3T3 feeder layer .

Project description:human corneal epithelial cells were isolated from healthy human donor eyes. Cells were cultured with irradiated 3T3 (i3T3) murine fibroblast feeder cells, irradiated human corneal fibroblasts (iHFL) or without feeder layer

2019-12-12 | GSE141841 | GEO

Targeting HIF-2α in skeletal progenitors and their descendants for the radioprotection of bone

Project description:Radiotherapy continues to be a common treatment modality for cancer despite skeletal complications. Currently, there are no effective treatments for radiation-induced bone loss. Radiation induces substantial changes to the bone microenvironment; however, the effects of these changes on skeletal progenitors and their descendants remain elusive. Following radiation, LeprCre skeletal progenitors and their descendants, localize to hypoxic regions and exhibit HIF-2α stabilization, thus implicating a role for HIF-2α in radiation-induced bone loss. To test whether HIF-2α deficiency rescues radiation-induced bone loss, we conditionally ablated HIF-2α in LeprCre-expressing cells and their descendants. Compared to irradiated controls, irradiated LeprCre;Hif-2αfl/fl knock out mice demonstrate increased bone mass with values comparable to non-irradiated animals. Mechanistically, HIF-2α negatively regulates osteoblastogenesis, mineralization, and number of skeletal progenitors. To test whether HIF-2α can be targeted therapeutically, we administered PT2399, a potent and selective HIF-2α inhibitor whose structural analog belzutifan, has recently received FDA approval. Administration of PT2399 was sufficient to prevent radiation-induced bone loss in a single-limb irradiation model. As ~90% of patients on HIF-2α inhibitor treatment develop anemia, we constructed a PT2399-loaded bone-targeting nanocarrier (Aln-PT-NC) to increase on-target efficacy and reduce off-target kidney toxicity. Delivery of Aln-PT-NC completely prevented radiation-induced bone loss while reducing drug accumulation in the kidney. In this study, we identify HIF-2α as a negative regulator of bone formation in LeprCre skeletal progenitors and their descendants following radiotherapy and developed a bone-targeting HIF-2α therapeutic. Together, these studies highlight the clinical potential of Aln-PT-NC to be translated into a treatment regimen for bone radioprotection.

2023-06-24 | GSE235292 | GEO

High complexity cellular barcoding and clonal tracing reveals stochastic and deterministic parameters of radiation resistance - Photon Irradiated samples

Project description:It is elusive whether clonal selection of tumor cells in response to ionizing radiation (IR) is a deterministic or stochastic process. With high resolution clonal barcoding and tracking of over 400.000 HNSCC patient-derived tumor cells the clonal dynamics of tumor cells in response to IR was analysed. Fractionated IR induced a strong selective pressure for clonal reduction. This significantly exceeded uniform clonal survival probabilities indicative for a strong clone-to clone difference. within tumor cells. Survival to IR is driven by a deterministic clonal selection of a smaller population which commonly survives radiation, while increased clonogenic capacity is a result of clonal competition of cells which have been selected stochastically. The ratio of these parameters is amenable to radiation sensitivity which correlates to prognostic biomarkers of HNSCC. Evidence for the existence of a rare subpopulation with an intrinsically radiation resistant phenotype was found at a frequency of 0.6-3.3%. With cellular barcoding we introduce a novel functional heterogeneity associated qualitative readout for evaluating the contribution of stochastic and deterministic clonal selection processes in response to IR. To analyze transcriptomic changes of HNSCC cell lines after fractionated Photon IR (5x4Gy), RNAseq analysis was performed on irradiated cells in comparison to untreated control cells (EBI submission E-MTAB-9693)

2021-08-31 | E-MTAB-10685 | biostudies-arrayexpress

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