ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

Skamagki, Maria; Correia, Cristina; Yeung, Percy Luk; Baslan, Timour; Beck, Samuel J.; Zhang, Cheng; Roß, Christian; Dang, Lam; Liu, Zhong; Giunta, Simona; Chang, Tzu Pei; Wang, Joye; Ananthanarayanan, Aparna; Bohndorf, Martina; Bosbach, Benedikt; Adjaye, James; Funabiki, Hironori; Kim, Jonghwan; Lowe, Scott W.; Collins, James J.; Lu, Chi Wei; Li, Hu; Zhao, Rui; Kim, Kitai

doi:10.1038/ncb3598

Cited by 36 publications

(38 citation statements)

References 64 publications

(92 reference statements)

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“…Comparative analyses of rodent and primate EPI defines conserved core pluripotency factors, in addition to POU5F1, SOX2 and NANOG. These include TFCP2L1 (Martello et al, 2013;Ye et al, 2013), ZSCAN10, shown to promote genomic stability in mouse embryonic stem cells (Skamagki et al, 2017), ZNF296, a component of heterochromatin (Matsuura et al, 2017) reported to enhance reprogramming efficiency (Fischedick et al, 2012) and interact with KLF4 (Fujii et al, 2013), ZFP36L1, a zinc-finger RNA-binding protein attenuating protein synthesis (Stoecklin et al, 2002) and…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development

Boroviak

Stirparo

Dietmann

et al. 2018

Preprint

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The mouse embryo is the canonical model for mammalian preimplantation development. Recent advances in single-cell profiling allow detailed analysis of embryogenesis in other eutherian species, including human, to distinguish conserved from divergent regulatory programs and signalling pathways in the rodent paradigm. Here, we identify and compare transcriptional features of human, marmoset and mouse embryos by single-cell RNA-seq. Zygotic genome activation correlates with the presence of Polycomb Repressive Complexes in all three species, while ribosome biogenesis emerges as a predominant attribute in primate embryos, supporting prolonged translation of maternally deposited RNAs. We find that transposable element expression signatures are species-, stage-and lineage-specific. The pluripotency network in the primate epiblast lacks certain regulators operative in mouse, but encompasses WNT components and genes associated with trophoblast specification. Sequential activation of GATA6, SOX17 and GATA4 markers of primitive endoderm identity is conserved in primates. Unexpectedly, OTX2 is also associated with primitive endoderm specification in human and nonhuman primate blastocysts. Our cross-species analysis demarcates both conserved and primate-specific features of preimplantation development and underscores the molecular adaptability of early mammalian embryogenesis.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development

Boroviak

Stirparo

Dietmann

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…Although ROS is detrimental to genomic stability, certain level of ROS is also essential to signal cellular stress and to induce DNA damage response (Skamagki et al 2017). ROS can directly oxidize ATM to activate this kinase and elicit ATM-mediated DNA damage response (Guo et al 2010).…”

Section: Glucose Metabolism In Pscsmentioning

confidence: 99%

“…To maintain the homeostasis between ROS and glutathione, PSCs express specific transcription factor Zscan10, which binds to the promoter of glutathione synthetase (GSS) and suppresses its transcription. Inadequate induction of Zscan10 in iPSCs will result in the excessive expression of GSS and the disruption of homeostasis between ROS and glutathione, leading to the genomic instability (Skamagki et al 2017).…”

Section: Glucose Metabolism In Pscsmentioning

confidence: 99%

Maintaining genomic stability in pluripotent stem cells

Zheng

2019

GENOME INSTAB. DIS.

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Pluripotent stem cells (PSCs) are capable of generating all types of cells in the body and have promising applications in basic research and cell-based regenerative medicine. Compared to the differentiated cells, PSCs are superior in maintaining genomic stability. However, the underlying molecular mechanisms are far from clear. Here, we summarized the understandings on the molecules and pathways that PSCs specifically utilize to cope with DNA replication-associated stress, to repair DNA damages and to determine cell fates.

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“…After constricted migration, nuclear oxidative stress is ~30% higher based on labeling by a redox dye ( Fig.3A). We therefore added a membrane-permeable antioxidant, glutathione, as a reduced monoethyl ester (GSH-MEE) that reduces H2O2-induced DNA damage in 2D cultures (Fig.3A, S2A); GSH-MEE has likewise been shown to reduce oxidative stress and genomic instability in pluripotent stem cells in 2D cultures (Skamagki et al, 2017). Partial rescue of DNA damage by GSH-MEE does not affect migrated cell numbers or nuclear blebs ( Fig.3B,C).…”

Section: Overexpressed Dna Repair Factors or Added Antioxidant Rescuementioning

confidence: 99%

Rescue of DNA damage in cells after constricted migration reveals bimodal mechano-regulation of cell cycle

Xia

Pfeifer

Zhu

et al. 2018

Preprint

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Migration through constrictions can clearly rupture nuclei and mis-localize nuclear proteins but damage to DNA remains uncertain as does any effect on cell cycle. Here, myosin-II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent delay in cell cycle is unaffected. Co-overexpression of multiple DNA repair factors and antioxidant inhibition of break formation also have partial effects, independent of rupture. However, there seems to be a bimodal dependence of cell cycle on DNA damage.Migration through custom-etched pores yields the same bimodal, with ~4-m pores causing intermediate levels of damage and cell cycle delay. Micronuclei (generated in faulty division) of the smallest diameter appear similar to ruptured nuclei, with high DNA damage and entry of chromatin-binding cGAS (cyclic-GMP-AMP-synthase) from cytoplasm but low repair factor levels. Increased genomic variation after constricted migration is quantified in expanding clones and is consistent with (mis)repair of excess DNA damage and subsequent proliferation.(161 words)

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ZSCAN10 expression corrects the genomic instability of iPSCs from aged donors

Cited by 36 publications

References 64 publications

Single-cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development

Single-cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development

Maintaining genomic stability in pluripotent stem cells

Rescue of DNA damage in cells after constricted migration reveals bimodal mechano-regulation of cell cycle

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