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A quantitative system for discriminating induced pluripotent stem cells, embryonic stem cells and somatic cells.

ABSTRACT: Induced pluripotent stem cells (iPSCs) derived from somatic cells (SCs) and embryonic stem cells (ESCs) provide promising resources for regenerative medicine and medical research, leading to a daily identification of new cell lines. However, an efficient system to discriminate the different types of cell lines is lacking. Here, we develop a quantitative system to discriminate the three cell types, iPSCs, ESCs, and SCs. The system consists of DNA-methylation biomarkers and mathematical models, including an artificial neural network and support vector machines. All biomarkers were unbiasedly selected by calculating an eigengene score derived from analysis of genome-wide DNA methylations. With 30 biomarkers, or even with as few as 3 top biomarkers, this system can discriminate SCs from pluripotent cells (PCs, including ESCs and iPSCs) with almost 100% accuracy. With approximately 100 biomarkers, the system can distinguish ESCs from iPSCs with an accuracy of 95%. This robust system performs precisely with raw data without normalization as well as with converted data in which the continuous methylation levels are accounted. Strikingly, this system can even accurately predict new samples generated from different microarray platforms and the next-generation sequencing. The subtypes of cells, such as female and male iPSCs and fetal and adult SCs, can also be discriminated with this method. Thus, this novel quantitative system works as an accurate framework for discriminating the three cell types, iPSCs, ESCs, and SCs. This strategy also supports the notion that DNA-methylation generally varies among the three cell types.

SUBMITTER: Wang A

PROVIDER: S-EPMC3572019 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A quantitative system for discriminating induced pluripotent stem cells, embryonic stem cells and somatic cells.

Wang Anyou A Du Ying Y He Qianchuan Q Zhou Chunxiao C

PloS one 20130213 2

Induced pluripotent stem cells (iPSCs) derived from somatic cells (SCs) and embryonic stem cells (ESCs) provide promising resources for regenerative medicine and medical research, leading to a daily identification of new cell lines. However, an efficient system to discriminate the different types of cell lines is lacking. Here, we develop a quantitative system to discriminate the three cell types, iPSCs, ESCs, and SCs. The system consists of DNA-methylation biomarkers and mathematical models, in ...[more]

PMID: 23418520

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Project description:BackgroundInduced pluripotent stem (iPS) cells have the capability to undergo self-renewal and differentiation into all somatic cell types. Since they can be produced through somatic cell reprogramming, which uses a defined set of transcription factors, iPS cells represent important sources of patient-specific cells for clinical applications. However, before these cells can be used in therapeutic designs, it is essential to understand their genetic stability.Methodology/principal findingsHere, we describe DNA damage responses in human iPS cells. We observe hypersensitivity to DNA damaging agents resulting in rapid induction of apoptosis after ?-irradiation. Expression of pluripotency factors does not appear to be diminished after irradiation in iPS cells. Following irradiation, iPS cells activate checkpoint signaling, evidenced by phosphorylation of ATM, NBS1, CHEK2, and TP53, localization of ATM to the double strand breaks (DSB), and localization of TP53 to the nucleus of NANOG-positive cells. We demonstrate that iPS cells temporary arrest cell cycle progression in the G(2) phase of the cell cycle, displaying a lack of the G(1)/S cell cycle arrest similar to human embryonic stem (ES) cells. Furthermore, both cell types remove DSB within six hours of ?-irradiation, form RAD51 foci and exhibit sister chromatid exchanges suggesting homologous recombination repair. Finally, we report elevated expression of genes involved in DNA damage signaling, checkpoint function, and repair of various types of DNA lesions in ES and iPS cells relative to their differentiated counterparts.Conclusions/significanceHigh degrees of similarity in DNA damage responses between ES and iPS cells were found. Even though reprogramming did not alter checkpoint signaling following DNA damage, dramatic changes in cell cycle structure, including a high percentage of cells in the S phase, increased radiosensitivity and loss of DNA damage-induced G(1)/S cell cycle arrest, were observed in stem cells generated by induced pluripotency.

Dataset Information

A quantitative system for discriminating induced pluripotent stem cells, embryonic stem cells and somatic cells.

Publications

A quantitative system for discriminating induced pluripotent stem cells, embryonic stem cells and somatic cells.

Similar Datasets

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