Human Embryonic Stem Cell Responses to Ionizing Radiation Exposures: Current State of Knowledge and Future Challenges

Overview

Journal Stem Cells Int

Publisher Wiley

Specialty Cell Biology

Date 2012 Sep 12

PMID 22966236

Citations 13

Authors

Mykyta V Sokolov

Ronald D Neumann

Affiliations

Soon will be listed here.

Abstract

Human embryonic stem cells, which are derived from the inner cell mass of the blastocyst, have become an object of intense study over the last decade. They possess two unique properties that distinguish them from many other cell types: (i) the ability to self-renew indefinitely in culture under permissive conditions, and (ii) the pluripotency, defined as the capability of giving rise to all cell types of embryonic lineage under the guidance of the appropriate developmental cues. The focus of many recent efforts has been on the elucidating the signaling pathways and molecular networks operating in human embryonic stem cells. These cells hold great promise in cell-based regenerative therapies, disease modeling, drug screening and testing, assessing genotoxic and mutagenic risks associated with exposures to a variety of environmental factors, and so forth. Ionizing radiation is ubiquitous in nature, and it is widely used in diagnostic and therapeutic procedures in medicine. In this paper, our goal is to summarize the recent progress in understanding how human embryonic stem cells respond to ionizing radiation exposures, using novel methodologies based on "omics" approaches, and to provide a critical discussion of what remains unknown; thus proposing a roadmap for the future research in this area.

Citing Articles

Evaluation of Changes in Some Functional Properties of Human Mesenchymal Stromal Cells Induced by Low Doses of Ionizing Radiation.

Usupzhanova D, Astrelina T, Kobzeva I, Suchkova Y, Brunchukov V, Rastorgueva A Int J Mol Sci. 2023; 24(7).

PMID: 37047317 PMC: 10094729. DOI: 10.3390/ijms24076346.

Constitutive High Expression of NOXA Sensitizes Human Embryonic Stem Cells for Rapid Cell Death.

Basundra R, Kapoor S, Hollville E, Kiapour N, Beltran Lopez A, Marie Melchiorre N Stem Cells. 2022; 40(1):49-58.

PMID: 35511861 PMC: 9199843. DOI: 10.1093/stmcls/sxab008.

Prospects for Radiopharmaceuticals as Effective and Safe Therapeutics in Oncology and Challenges of Tumor Resistance to Radiotherapy.

Nikolova E, Tonev D, Zhelev N, Neychev V Dose Response. 2021; 19(1):1559325821993665.

PMID: 33716590 PMC: 7923993. DOI: 10.1177/1559325821993665.

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.

Fabbrizi M, Warshowsky K, Zobel C, Hallahan D, Sharma G Cell Death Discov. 2018; 4:117.

PMID: 30588339 PMC: 6299079. DOI: 10.1038/s41420-018-0132-8.

Recruitment kinetics of the homologous recombination pathway in procyclic forms of Trypanosoma brucei after ionizing radiation treatment.

Marin P, Silva M, Pavani R, Machado C, Elias M Sci Rep. 2018; 8(1):5405.

PMID: 29599445 PMC: 5876374. DOI: 10.1038/s41598-018-23731-6.

References

Daza P, Schubler H, McMILLAN T, Girod S, Pfeiffer P . Radiosensitivity and double-strand break rejoining in tumorigenic and non-tumorigenic human epithelial cell lines. Int J Radiat Biol. 1997; 72(1):91-100. DOI: 10.1080/095530097143572. View

Becker K, Ghule P, Lian J, Stein J, van Wijnen A, Stein G . Cyclin D2 and the CDK substrate p220(NPAT) are required for self-renewal of human embryonic stem cells. J Cell Physiol. 2009; 222(2):456-64. PMC: 3059841. DOI: 10.1002/jcp.21967. View

Shamblott M, Axelman J, Wang S, Bugg E, LITTLEFIELD J, Donovan P . Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci U S A. 1998; 95(23):13726-31. PMC: 24887. DOI: 10.1073/pnas.95.23.13726. View

Becher U, Breitbach M, Sasse P, Garbe S, van der Ven P, Furst D . Enrichment and terminal differentiation of striated muscle progenitors in vitro. Exp Cell Res. 2009; 315(16):2741-51. DOI: 10.1016/j.yexcr.2009.07.005. View

Dumitru R, Gama V, Fagan B, Bower J, Swahari V, Pevny L . Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis. Mol Cell. 2012; 46(5):573-83. PMC: 3372694. DOI: 10.1016/j.molcel.2012.04.002. View

Wilson 3rd D, Kim D, Berquist B, Sigurdson A . Variation in base excision repair capacity. Mutat Res. 2010; 711(1-2):100-12. PMC: 3101302. DOI: 10.1016/j.mrfmmm.2010.12.004. View

Ghule P, Dominski Z, Yang X, Marzluff W, Becker K, Harper J . Staged assembly of histone gene expression machinery at subnuclear foci in the abbreviated cell cycle of human embryonic stem cells. Proc Natl Acad Sci U S A. 2008; 105(44):16964-9. PMC: 2579361. DOI: 10.1073/pnas.0809273105. View

Lieber M . The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010; 79:181-211. PMC: 3079308. DOI: 10.1146/annurev.biochem.052308.093131. View

Moynahan M, Jasin M . Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol. 2010; 11(3):196-207. PMC: 3261768. DOI: 10.1038/nrm2851. View

10.

Allegrucci C, Young L . Differences between human embryonic stem cell lines. Hum Reprod Update. 2006; 13(2):103-20. DOI: 10.1093/humupd/dml041. View

11.

Kudriashov I . [Main principles of radiobiology]. Radiats Biol Radioecol. 2001; 41(5):531-47. View

12.

Hamada N, Matsumoto H, Hara T, Kobayashi Y . Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects. J Radiat Res. 2007; 48(2):87-95. DOI: 10.1269/jrr.06084. View

13.

Svilar D, Goellner E, Almeida K, Sobol R . Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage. Antioxid Redox Signal. 2010; 14(12):2491-507. PMC: 3096496. DOI: 10.1089/ars.2010.3466. View

14.

Dolezalova D, Mraz M, Barta T, Plevova K, Vinarsky V, Holubcova Z . MicroRNAs regulate p21(Waf1/Cip1) protein expression and the DNA damage response in human embryonic stem cells. Stem Cells. 2012; 30(7):1362-72. DOI: 10.1002/stem.1108. View

15.

Mothersill C, Seymour C . Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int J Radiat Biol. 1997; 71(4):421-7. DOI: 10.1080/095530097144030. View

16.

Rodningen O, Overgaard J, Alsner J, Hastie T, Borresen-Dale A . Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts. Radiother Oncol. 2005; 77(3):231-40. DOI: 10.1016/j.radonc.2005.09.020. View

17.

Sokolov M, Panyutin I, Neumann R . Unraveling the global microRNAome responses to ionizing radiation in human embryonic stem cells. PLoS One. 2012; 7(2):e31028. PMC: 3275573. DOI: 10.1371/journal.pone.0031028. View

18.

Mattout A, Meshorer E . Chromatin plasticity and genome organization in pluripotent embryonic stem cells. Curr Opin Cell Biol. 2010; 22(3):334-41. DOI: 10.1016/j.ceb.2010.02.001. View

19.

King F, Ritner C, Liszewski W, Kwan H, Pedersen A, Leavitt A . Subpopulations of human embryonic stem cells with distinct tissue-specific fates can be selected from pluripotent cultures. Stem Cells Dev. 2009; 18(10):1441-50. PMC: 2939715. DOI: 10.1089/scd.2009.0012. View

20.

Mantel C, Guo Y, Lee M, Kim M, Han M, Shibayama H . Checkpoint-apoptosis uncoupling in human and mouse embryonic stem cells: a source of karyotpic instability. Blood. 2007; 109(10):4518-27. PMC: 1885509. DOI: 10.1182/blood-2006-10-054247. View