Gene expression after low dose irradiation in pluripotent stem cells developing to retinal ganglion cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE158543 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:The effects of low dose irradiation on the gene expression on the neural cell development using human induced pluripotent stem cells (hiPS cells).
2020-12-26 | GSE142658 | GEO
Project description:Gene expression after low dose irradiation in pluripotent stem cells developing to retinal ganglion cells
| PRJNA665538 | ENA
Project description:Gene expression after low dose irradiation in pluripotent stem cells developing to retinal ganglion cells
| PRJNA597881 | ENA
Project description:Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy. However, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. Here we show that limited low dose irradiation (LDI) using either γ-ray or X-ray exposure (0.4 Gy) significantly enhances HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, Histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by over 30- fold when combined with the targeting tools zinc finger nucleases (ZFNs), transcription activator–like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPRs). Whole exome sequencing confirmed that the LDI to hPSCs did not induce gross genomic alterations, or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new targeted hPSC lines that are crucial for the research community as this growing field develops.
2016-03-22 | GSE68328 | GEO
Project description:Human pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy. However, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. Here we show that limited low dose irradiation (LDI) using either γ-ray or X-ray exposure (0.4 Gy) significantly enhances HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, Histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by over 30- fold when combined with the targeting tools zinc finger nucleases (ZFNs), transcription activatorâ??like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPRs). Whole exome sequencing confirmed that the LDI to hPSCs did not induce gross genomic alterations, or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new targeted hPSC lines that are crucial for the research community as this growing field develops. 4 samples
2016-03-22 | E-GEOD-68328 | biostudies-arrayexpress
Project description:UnlabelledHuman pluripotent stem cells (hPSCs) are now being used for both disease modeling and cell therapy; however, efficient homologous recombination (HR) is often crucial to develop isogenic control or reporter lines. We showed that limited low-dose irradiation (LDI) using either γ-ray or x-ray exposure (0.4 Gy) significantly enhanced HR frequency, possibly through induction of DNA repair/recombination machinery including ataxia-telangiectasia mutated, histone H2A.X and RAD51 proteins. LDI could also increase HR efficiency by more than 30-fold when combined with the targeting tools zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats. Whole-exome sequencing confirmed that the LDI administered to hPSCs did not induce gross genomic alterations or affect cellular viability. Irradiated and targeted lines were karyotypically normal and made all differentiated lineages that continued to express green fluorescent protein targeted at the AAVS1 locus. This simple method allows higher throughput of new, targeted hPSC lines that are crucial to expand the use of disease modeling and to develop novel avenues of cell therapy.SignificanceThe simple and relevant technique described in this report uses a low level of radiation to increase desired gene modifications in human pluripotent stem cells by an order of magnitude. This higher efficiency permits greater throughput with reduced time and cost. The low level of radiation also greatly increased the recombination frequency when combined with developed engineered nucleases. Critically, the radiation did not lead to increases in DNA mutations or to reductions in overall cellular viability. This novel technique enables not only the rapid production of disease models using human stem cells but also the possibility of treating genetically based diseases by correcting patient-derived cells.
| S-EPMC4542875 | biostudies-literature
Project description:The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4-5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the "development of neurons" pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.
| S-EPMC10412642 | biostudies-literature
Project description:Caesium-137 (Cs-137) is one of the major radionuclides appearing in the natural environment after nuclear power plant accidents. However, the biological effects of low-dose internal irradiation with this radionuclide remain unclear. We developed an experimental model for studying low-dose internal irradiation using cultured human cells. The cells were incubated in the culture medium supplemented with unsealed Cs-137 chloride. We used the Monte Carlo simulation method for measuring internal irradiation because making direct measurements was not possible. The simulation revealed that 96.40%?99.70% of the internal irradiation involved ?-particles and other electrons. During the experiment, a gradual incorporation of Cs-137 in the cells, and the absorbed dose rate increased in a time-dependent manner. In addition, the number of ?-H2AX and 53BP1 nuclear foci in the cells increased by internal irradiation in a dose-dependent manner. Microarray analysis revealed time-dependent alterations in gene expression caused by the radiation. These results demonstrate that our experimental system can be useful in the investigation of the effects of low-dose internal irradiation.
2015-03-15 | GSE66720 | GEO
Project description:Transcriptome analysis of irradiated T evansi parasites The protozoan parasite Trypanosoma evansi is responsible for causing Surra in a variety of mammalian hosts over a wide geographical area. In order to identify which genes and processes are required to establish disease in mice, parasites were irradiated over a range using a Cobalt60 gamma source. A custom Trypanosome spp. array that covers the genomes of three trypanosome species, T. brucei, T. evansi and T. congolense was designed by Affymetrix with an average of 9300 whole gene transcripts from all three species were targeted. Irradiation differentially affected the abundance of gene transcripts in a dose-dependent trend. We present these genes as necessary for repair from irradiation damage, and essential for disease establishment in mice post irradiation.
2023-05-06 | GSE202334 | GEO
Project description:Transcriptomic profiling of normal mouse tissue following 131I irradiation.
2012-05-18 | GSE32014 | GEO