Brackmann, Lara Kim ; Poplawski, Alicia ; Grandt, Caine Lucas ; Schwarz, Heike ; Hankeln, Thomas ; Rapp, Steffen ; Zahnreich, Sebastian ; Galetzka, Danuta ; Schmitt, Iris ; Grad, Christian ; Eckhard, Lukas ; Mirsch, Johanna ; Blettner, Maria ; Scholz-Kreisel, Peter ; Hess, Moritz ; Binder, Harald ; Schmidberger, Heinz ; Marron, Manuela (2020)
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation.
In: Molecular Medicine, 26 (1)
doi: 10.1186/s10020-020-00203-0
Artikel, Bibliographie
Dies ist die neueste Version dieses Eintrags.
Kurzbeschreibung (Abstract)
Background: Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points.
Methods: Fibroblasts from skin biopsies of 15 cell donors were exposed to a high (2Gy) and a low (0.05Gy) dose of X-rays. RNA was extracted and sequenced 2 h and 4 h after exposure. Differentially expressed genes with an adjusted p-value < 0.05 were flagged and used for pathway analyses including prediction of upstream and downstream effects. Principal component analyses were used to examine the effect of two different sequencing runs on quality metrics and variation in expression and alignment and for explorative analysis of the radiation dose and time point of analysis.
Results: More genes were differentially expressed 4 h after exposure to low and high doses of radiation than after 2 h. In experiments with high dose irradiation and RNA sequencing after 4 h, inactivation of the FAT10 cancer signaling pathway and activation of gluconeogenesis I, glycolysis I, and prostanoid biosynthesis was observed taking p-value (< 0.05) and (in) activating z-score (≥2.00 or ≤ − 2.00) into account. Two hours after high dose irradiation, inactivation of small cell lung cancer signaling was observed. For low dose irradiation experiments, we did not detect any significant (p < 0.05 and z-score ≥ 2.00 or ≤ − 2.00) activated or inactivated pathways for both time points.
Conclusions: Compared to 2 h after irradiation, a higher number of differentially expressed genes were found 4 h after exposure to low and high dose ionizing radiation. Differences in gene expression were related to signal transduction pathways of the DNA damage response after 2 h and to metabolic pathways, that might implicate cellular senescence, after 4 h. The time point 4 h will be used to conduct further irradiation experiments in a larger sample.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2020 |
| Autor(en): | Brackmann, Lara Kim ; Poplawski, Alicia ; Grandt, Caine Lucas ; Schwarz, Heike ; Hankeln, Thomas ; Rapp, Steffen ; Zahnreich, Sebastian ; Galetzka, Danuta ; Schmitt, Iris ; Grad, Christian ; Eckhard, Lukas ; Mirsch, Johanna ; Blettner, Maria ; Scholz-Kreisel, Peter ; Hess, Moritz ; Binder, Harald ; Schmidberger, Heinz ; Marron, Manuela |
| Art des Eintrags: | Bibliographie |
| Titel: | Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation |
| Sprache: | Englisch |
| Publikationsjahr: | 9 September 2020 |
| Ort: | London |
| Verlag: | BioMed Central |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Molecular Medicine |
| Jahrgang/Volume einer Zeitschrift: | 26 |
| (Heft-)Nummer: | 1 |
| Kollation: | 13 Seiten |
| DOI: | 10.1186/s10020-020-00203-0 |
| Zugehörige Links: | |
| Kurzbeschreibung (Abstract): | Background: Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods: Fibroblasts from skin biopsies of 15 cell donors were exposed to a high (2Gy) and a low (0.05Gy) dose of X-rays. RNA was extracted and sequenced 2 h and 4 h after exposure. Differentially expressed genes with an adjusted p-value < 0.05 were flagged and used for pathway analyses including prediction of upstream and downstream effects. Principal component analyses were used to examine the effect of two different sequencing runs on quality metrics and variation in expression and alignment and for explorative analysis of the radiation dose and time point of analysis. Results: More genes were differentially expressed 4 h after exposure to low and high doses of radiation than after 2 h. In experiments with high dose irradiation and RNA sequencing after 4 h, inactivation of the FAT10 cancer signaling pathway and activation of gluconeogenesis I, glycolysis I, and prostanoid biosynthesis was observed taking p-value (< 0.05) and (in) activating z-score (≥2.00 or ≤ − 2.00) into account. Two hours after high dose irradiation, inactivation of small cell lung cancer signaling was observed. For low dose irradiation experiments, we did not detect any significant (p < 0.05 and z-score ≥ 2.00 or ≤ − 2.00) activated or inactivated pathways for both time points. Conclusions: Compared to 2 h after irradiation, a higher number of differentially expressed genes were found 4 h after exposure to low and high dose ionizing radiation. Differences in gene expression were related to signal transduction pathways of the DNA damage response after 2 h and to metabolic pathways, that might implicate cellular senescence, after 4 h. The time point 4 h will be used to conduct further irradiation experiments in a larger sample. |
| Freie Schlagworte: | Childhood cancer, Fibroblasts, Gene-radiation interaction, High dose, Ionizing radiation, IPA, Low dose, RNA sequencing, Second primary neoplasm |
| ID-Nummer: | Artikel-ID: 85 |
| Zusätzliche Informationen: | Part of Springer Nature |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Radiation Biology and DNA Repair |
| Hinterlegungsdatum: | 04 Okt 2024 08:28 |
| Letzte Änderung: | 04 Okt 2024 08:28 |
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| Suche nach Titel in: | TUfind oder in Google |
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Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation. (deposited 30 Sep 2024 08:29)
- Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation. (deposited 04 Okt 2024 08:28) [Gegenwärtig angezeigt]
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