scholarly journals Influence ofATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells

2016 ◽  
Vol 25 (9) ◽  
pp. 740-747 ◽  
Author(s):  
Junjie Lu ◽  
Hu Li ◽  
Anna Baccei ◽  
Takayo Sasaki ◽  
David M. Gilbert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Induced Pluripotent Stem Cells ◽  
Dna Damage Response ◽  
Pluripotent Stem Cells ◽  
Genomic Variation ◽  
Damage Response ◽  
Induced Pluripotent

scholarly journals DNA Damage Response in Neonatal and Adult Stromal Cells Compared With Induced Pluripotent Stem Cells

2015 ◽  
Vol 4 (6) ◽  
pp. 576-589 ◽  
Author(s):  
Stefanie Liedtke ◽  
Sophie Biebernick ◽  
Teja Falk Radke ◽  
Daniela Stapelkamp ◽  
Carolin Coenen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Induced Pluripotent Stem Cells ◽  
Dna Damage Response ◽  
Stromal Cells ◽  
Pluripotent Stem Cells ◽  
Damage Response ◽  
Induced Pluripotent

scholarly journals Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells

2019 ◽  
Vol 60 (6) ◽  
pp. 719-728 ◽  
Author(s):  
Mikio Shimada ◽  
Kaima Tsukada ◽  
Nozomi Kagawa ◽  
Yoshihisa Matsumoto
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Induced Pluripotent Stem Cells ◽  
Dna Damage Response ◽  
Pluripotent Stem Cells ◽  
Genome Stability ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Transcriptional Change ◽  
Damage Response ◽  
Induced Pluripotent

Abstract Pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have a dual capability to self-renew and differentiate into all cell types necessary to develop an entire organism. Differentiation is associated with dynamic epigenetic alteration and transcriptional change, while self-renewal depends on maintaining the genome DNA accurately. Genome stability of PSCs is strictly regulated to maintain pluripotency. However, the DNA damage response (DDR) mechanism in PSCs is still unclear. There is accumulating evidence that genome stability and pluripotency are regulated by a transcriptional change in undifferentiated and differentiated states. iPSCs are ideal for analyzing transcriptional regulation during reprogramming and differentiation. This study aimed to elucidate the transcriptional alteration surrounding genome stability maintenance, including DNA repair, cell cycle checkpoints and apoptosis in fibroblasts, iPSCs and neural progenitor cells (NPCs) derived from iPSCs as differentiated cells. After ionizing radiation exposure, foci for the DNA double-stranded break marker γ-H2AX increased, peaking at 0.5 h in all cells (>90%), decreasing after 4 h in fibroblasts (32.3%) and NPCs (22.3%), but still remaining at 52.5% (NB1RGB C2 clone) and 54.7% (201B7 cells) in iPSCs. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells were detected, indicating that iPSCs’ apoptosis increases. In addition, RNA sequencing (RNA-Seq) analysis showed high expression of apoptosis genes (TP53, CASP3 and BID) in iPSCs. Results suggested that increased apoptosis activity maintains accurate, undifferentiated genome DNA in the cell population.

scholarly journals Pluripotent Stem Cells and DNA Damage Response to Ionizing Radiations

2016 ◽  
Vol 186 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Kalpana Mujoo ◽  
E. Brian Butler ◽  
Raj K. Pandita ◽  
Clayton R. Hunt ◽  
Tej K. Pandita
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Pluripotent Stem Cells ◽  
Damage Response ◽  
Ionizing Radiations

scholarly journals Induced Pluripotent Stem Cells Are Sensitive to DNA Damage

2013 ◽  
Vol 11 (5) ◽  
pp. 320-326 ◽  
Author(s):  
Minjie Zhang ◽  
Caiyun Yang ◽  
Huixian Liu ◽  
Yingli Sun
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

scholarly journals DNA Damage Responses in Human Induced Pluripotent Stem Cells and Embryonic Stem Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (10) ◽  
pp. e13410 ◽  
Author(s):  
Olga Momcilovic ◽  
Leah Knobloch ◽  
Jamie Fornsaglio ◽  
Sandra Varum ◽  
Charles Easley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Embryonic Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Dna Damage Responses ◽  
Induced Pluripotent

scholarly journals Ronin influences the DNA damage response in pluripotent stem cells

2017 ◽  
Vol 23 ◽  
pp. 98-104 ◽  
Author(s):  
Bryce A. Seifert ◽  
Marion Dejosez ◽  
Thomas P. Zwaka
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Pluripotent Stem Cells ◽  
Damage Response

scholarly journals Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

2021 ◽  
Author(s):  
Foad J Rouhani ◽  
Xueqing Zou ◽  
Petr Danecek ◽  
Tauanne Dias Amarante ◽  
Gene Koh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent Stem Cell ◽  
Specific Model ◽  
Genomic Variation ◽  
Patient Specific ◽  
Sequencing Data ◽  
Induced Pluripotent

SummaryHuman Induced Pluripotent Stem Cells (hiPSC) are an established patient-specific model system where opportunities are emerging for cell-based therapies. We contrast hiPSCs derived from different tissues, skin and blood, in the same individual. We show extensive single-nucleotide mutagenesis in all hiPSC lines, although fibroblast-derived hiPSCs (F-hiPSCs) are particularly heavily mutagenized by ultraviolet(UV)-related damage. We utilize genome sequencing data on 454 F-hiPSCs and 44 blood-derived hiPSCs (B-hiPSCs) to gain further insights. Across 324 whole genome sequenced(WGS) F-hiPSCs derived by the Human Induced Pluripotent Stem Cell Initiative (HipSci), UV-related damage is present in ~72% of cell lines, sometimes causing substantial mutagenesis (range 0.25-15 per Mb). Furthermore, we find remarkable genomic heterogeneity between independent F-hiPSC clones derived from the same reprogramming process in the same donor, due to oligoclonal populations within fibroblasts. Combining WGS and exome-sequencing data of 452 HipSci F-hiPSCs, we identify 272 predicted pathogenic mutations in cancer-related genes, of which 21 genes were hit recurrently three or more times, involving 77 (17%) lines. Notably, 151 of 272 mutations were present in starting fibroblast populations suggesting that more than half of putative driver events in F-hiPSCs were acquired in vivo. In contrast, B-hiPSCs reprogrammed from erythroblasts show lower levels of genome-wide mutations (range 0.28-1.4 per Mb), no UV damage, but a strikingly high prevalence of acquired BCOR mutations of ~57%, indicative of strong selection pressure. All hiPSCs had otherwise stable, diploid genomes on karyotypic pre-screening, highlighting how copy-number-based approaches do not have the required resolution to detect widespread nucleotide mutagenesis. This work strongly suggests that models for cell-based therapies require detailed nucleotide-resolution characterization prior to clinical application.

scholarly journals DNA Damage Response and Cell Cycle Regulation in Pluripotent Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1548
Author(s):  
Andy Chun Hang Chen ◽  
Qian Peng ◽  
Sze Wan Fong ◽  
Kai Chuen Lee ◽  
William Shu Biu Yeung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Genomic Stability ◽  
Great Promise ◽  
Cell Based Therapy ◽  
Damage Response

Pluripotent stem cells (PSCs) hold great promise in cell-based therapy because of their pluripotent property and the ability to proliferate indefinitely. Embryonic stem cells (ESCs) derived from inner cell mass (ICM) possess unique cell cycle control with shortened G1 phase. In addition, ESCs have high expression of homologous recombination (HR)-related proteins, which repair double-strand breaks (DSBs) through HR or the non-homologous end joining (NHEJ) pathway. On the other hand, the generation of induced pluripotent stem cells (iPSCs) by forced expression of transcription factors (Oct4, Sox2, Klf4, c-Myc) is accompanied by oxidative stress and DNA damage. The DNA repair mechanism of DSBs is therefore critical in determining the genomic stability and efficiency of iPSCs generation. Maintaining genomic stability in PSCs plays a pivotal role in the proliferation and pluripotency of PSCs. In terms of therapeutic application, genomic stability is the key to reducing the risks of cancer development due to abnormal cell replication. Over the years, we and other groups have identified important regulators of DNA damage response in PSCs, including FOXM1, SIRT1 and PUMA. They function through transcription regulation of downstream targets (P53, CDK1) that are involved in cell cycle regulations. Here, we review the fundamental links between the PSC-specific HR process and DNA damage response, with a focus on the roles of FOXM1 and SIRT1 on maintaining genomic integrity.

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