scholarly journals Genomic Instability of Pluripotent Stem Cells: Origin and Consequences

10.5772/62906 ◽  
2016 ◽  
Author(s):  
Elena Lo Furno ◽  
Siem van der Laan ◽  
Domenico Maiorano
Keyword(s):  
Stem Cells ◽  
Genomic Instability ◽  
Pluripotent Stem Cells

scholarly journals Elevated retrotransposon activity and genomic instability in primed pluripotent stem cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Haifeng Fu ◽  
Weiyu Zhang ◽  
Niannian Li ◽  
Jiao Yang ◽  
Xiaoying Ye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genomic Instability ◽  
Pluripotent Stem Cells ◽  
Molecular Mechanisms ◽  
Dna Recombination ◽  
Telomere Maintenance ◽  
Recombination Repair ◽  
Repair Activity ◽  
Retrotransposon Activity

Abstract Background Naïve and primed pluripotent stem cells (PSCs) represent two different pluripotent states. Primed PSCs following in vitro culture exhibit lower developmental potency as evidenced by failure in germline chimera assays, unlike mouse naïve PSCs. However, the molecular mechanisms underlying the lower developmental competency of primed PSCs remain elusive. Results We examine the regulation of telomere maintenance, retrotransposon activity, and genomic stability of primed PSCs and compare them with naïve PSCs. Surprisingly, primed PSCs only minimally maintain telomeres and show fragile telomeres, associated with declined DNA recombination and repair activity, in contrast to naïve PSCs that robustly elongate telomeres. Also, we identify LINE1 family integrant L1Md_T as naïve-specific retrotransposon and ERVK family integrant IAPEz to define primed PSCs, and their transcription is differentially regulated by heterochromatic histones and Dnmt3b. Notably, genomic instability of primed PSCs is increased, in association with aberrant retrotransposon activity. Conclusions Our data suggest that fragile telomere, retrotransposon-associated genomic instability, and declined DNA recombination repair, together with reduced function of cell cycle and mitochondria, increased apoptosis, and differentiation properties may link to compromised developmental potency of primed PSCs, noticeably distinguishable from naïve PSCs.

scholarly journals Comprehensive characterization of genomic instability in pluripotent stem cells and their derived neuroprogenitor cell lines

2012 ◽  
Vol 1 ◽  
pp. 21-24
Author(s):  
Nestor Luis Lopez Corrales ◽  
Kristin Mrasek ◽  
Martin Voigt ◽  
Thomas Liehr ◽  
Nadezda Kosyakova
Keyword(s):  
Stem Cells ◽  
Genomic Instability ◽  
Cell Lines ◽  
Pluripotent Stem Cells ◽  
Comprehensive Characterization

scholarly journals Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects

2016 ◽  
Vol 18 (2) ◽  
pp. 253-261 ◽  
Author(s):  
Noa Lamm ◽  
Uri Ben-David ◽  
Tamar Golan-Lev ◽  
Zuzana Storchová ◽  
Nissim Benvenisty ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genomic Instability ◽  
Pluripotent Stem Cells ◽  
Chromosome Condensation ◽  
Human Pluripotent Stem Cells ◽  
Replicative Stress

scholarly journals Genomic Instability Associated with p53 Knockdown in the Generation of Huntington’s Disease Human Induced Pluripotent Stem Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150372 ◽  
Author(s):  
Andrew M. Tidball ◽  
M. Diana Neely ◽  
Reed Chamberlin ◽  
Asad A. Aboud ◽  
Kevin K. Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Huntington's Disease ◽  
Induced Pluripotent Stem Cells ◽  
Huntington’S Disease ◽  
Genomic Instability ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals The propensity for tumorigenesis in human induced pluripotent stem cells is related with genomic instability

2013 ◽  
Vol 32 (4) ◽  
pp. 205-212 ◽  
Author(s):  
Yi Liang ◽  
Hui Zhang ◽  
Qi-Sheng Feng ◽  
Man-Bo Cai ◽  
Wen Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Genomic Instability ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 53 ◽  
Author(s):  
Sarka Jelinkova ◽  
Petr Fojtik ◽  
Aneta Kohutova ◽  
Aleksandra Vilotic ◽  
Lenka Marková ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Genomic Instability ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Pluripotent Stem Cell ◽  
Wild Type ◽  
Dystrophin Deficiency ◽  
Oxide Synthase

Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysregulated activity of all three isoforms of nitric oxide synthase (further abrev. as, NOS). NOS-induced ROS release leads to DNA damage and genomic instability in DMD hPSC. We were able to reduce both the ROS release as well as DNA damage to the level of wild-type hPSC by inhibiting NOS activity.

scholarly journals Pluripotent stem cells with low differentiation potential contain incompletely reprogrammed DNA replication

2020 ◽  
Vol 219 (9) ◽  
Author(s):  
Theodore Paniza ◽  
Madhura Deshpande ◽  
Ning Wang ◽  
Ryan O’Neil ◽  
Michael V. Zuccaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Genomic Instability ◽  
Single Molecule ◽  
Pluripotent Stem Cells ◽  
Dna Breaks ◽  
Differentiation Potential ◽  
Quality Control Tool ◽  
The Impact

Reprogrammed pluripotent stem cells (PSCs) are valuable for research and potentially for cell replacement therapy. However, only a fraction of reprogrammed PSCs are developmentally competent. Genomic stability and accurate DNA synthesis are fundamental for cell development and critical for safety. We analyzed whether defects in DNA replication contribute to genomic instability and the diverse differentiation potentials of reprogrammed PSCs. Using a unique single-molecule approach, we visualized DNA replication in isogenic PSCs generated by different reprogramming approaches, either somatic cell nuclear transfer (NT-hESCs) or with defined factors (iPSCs). In PSCs with lower differentiation potential, DNA replication was incompletely reprogrammed, and genomic instability increased during replicative stress. Reprogramming of DNA replication did not correlate with DNA methylation. Instead, fewer replication origins and a higher frequency of DNA breaks in PSCs with incompletely reprogrammed DNA replication were found. Given the impact of error-free DNA synthesis on the genomic integrity and differentiation proficiency of PSCs, analyzing DNA replication may be a useful quality control tool.

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