Reprogramming towards totipotency is greatly facilitated by synergistic effects of small molecules

Miyamoto, Kazuaki; Tajima, Yosuke; Yoshida, Koki; Oikawa, Mami; Azuma, Rika; Allen, George E.; Tsujikawa, Tomomi; Tsukaguchi, Tomomasa; Bradshaw, Charles R.; Jullien, Jérôme; Yamagata, Kazuya; Matsumoto, Kazuya; Anzai, Masayuki; Imai, Hiroshi; Gurdon, J. B.; Yamada, Masao

doi:10.1242/bio.023473

Cited by 31 publications

(49 citation statements)

References 61 publications

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“…The reprogramming of differentiated cells toward an embryonic state, which requires the remodeling of chromatin in order to break the epigenetic barriers and histone acetylation in concert with the methylation of histones and DNA are believed to play central roles in this process reviewed in Fehér (2015) and Horstman et al (2017a) . In support of the function of histone acetylation in cellular reprogramming, the inhibitor of HDACs – TSA – has been shown to improve embryo cloning in mammals ( Beigh et al, 2017 ; Miyamoto et al, 2017 ) and to promote somatic embryo development in Arabidopsis seedlings (Tanaka et al; 2008). Given that the TSA treatment was observed to have a distinct impact on gene expression in animals and plants ( Görisch et al, 2005 ; Chang and Pikaard, 2005 ; Inoue et al, 2015 ), the embryogenic response that is induced by TSA appears to result from the de-repression of the specific regulatory genes that control the embryogenic transition.…”

Section: Discussionmentioning

confidence: 99%

“…In mammals, TSA has been widely used to improve the nuclear reprogramming of somatic cells for embryo cloning ( Beigh et al, 2017 ; Miyamoto et al, 2017 ). Moreover, the TSA-induced inhibition of tumor growth and the apoptosis of cancer cells indicates the potential application of this drug in epigenetic therapy against cancer ( Damaskos et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Trichostatin A Triggers an Embryogenic Transition in Arabidopsis Explants via an Auxin-Related Pathway

et al. 2018

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Auxin is an important regulator of plant ontogenies including embryo development and the exogenous application of this phytohormone has been found to be necessary for the induction of the embryogenic response in plant explants that have been cultured in vitro. However, in the present study, we show that treatment of Arabidopsis explants with trichostatin A (TSA), which is a chemical inhibitor of histone deacetylases, induces somatic embryogenesis (SE) without the exogenous application of auxin. We found that the TSA-treated explants generated somatic embryos that developed efficiently on the adaxial side of the cotyledons, which are the parts of an explant that are involved in auxin-induced SE. A substantial reduction in the activity of histone deacetylase (HDAC) was observed in the TSA-treated explants, thus confirming a histone acetylation-related mechanism of the TSA-promoted embryogenic response. Unexpectedly, the embryogenic effect of TSA was lower on the auxin-supplemented media and this finding further suggests an auxin-related mechanism of TSA-induced SE. Congruently, we found a significantly increased content of indolic compounds, which is indicative of IAA and an enhanced DR5::GUS signal in the TSA-treated explants. In line with these results, two of the YUCCA genes (YUC1 and YUC10), which are involved in auxin biosynthesis, were found to be distinctly up-regulated during TSA-induced SE and their expression was colocalised with the explant sites that are involved in SE. Beside auxin, ROS were extensively accumulated in response to TSA, thereby indicating that a stress-response is involved in TSA-triggered SE. Relevantly, we showed that the genes encoding the transcription factors (TFs) that have a regulatory function in auxin biosynthesis including LEC1, LEC2, BBM, and stress responses (MYB118) were highly up-regulated in the TSA-treated explants. Collectively, the results provide several pieces of evidence about the similarities between the molecular pathways of SE induction that are triggered by TSA and 2,4-D that involve the activation of the auxin-responsive TF genes that have a regulatory function in auxin biosynthesis and stress responses. The study suggests the involvement of histone acetylation in the auxin-mediated release of the embryogenic program of development in the somatic cells of Arabidopsis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trichostatin A Triggers an Embryogenic Transition in Arabidopsis Explants via an Auxin-Related Pathway

et al. 2018

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“…Taken together, our results suggest that epigenetic reprogramming might be regulated under ROS conditions moderated by PRDX-mediated antioxidant mechanisms during the maternal-to-zygotic transition (MZT). Correspondingly, the observation that preventing oxidative stress is important for epigenetic reprogramming, is shown in a recent report, in which treatment with the antioxidant, vitamin C after exposure to the HDAC inhibitor, trichostatin A, dramatically improves cloning efficiency in somatic cell nuclear transfer (SCNT) embryos [ 56 ]. Further studies are needed to elucidate how PRDX-mediated antioxidant mechanisms are involved in epigenetic reprogramming during MZT.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin as a functional endogenous antioxidant enzyme in pronuclei of mouse zygotes

Morita

Tokoro²,

Hatanaka

et al. 2018

Journal of Reproduction and Development

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Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (H2O2). We here report the cellular localization of hyperoxidized PRDX and its involvement in the antioxidant mechanisms of freshly fertilized oocytes. Treatment of zygotes at the pronuclear stage with H2O2 enhanced pronuclear localization of hyperoxidized PRDX in zygotes and concurrently impaired the generation of 5-hydroxymethylcytosine (5hmC) on the male genome, which is an epigenetic reprogramming event that occurs at the pronuclear stage. Thus, our results suggest that endogenous PRDX is involved in antioxidant mechanisms and epigenetic reprogramming during MZT.

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“…The culture media used were potassium simplex optimized medium (KSOM medium) without EDTA and pyruvate supplemented with 0.3% deionized BSA (dBSA), designated here as ‐P medium, and ‐P medium with or without various concentrations (0.01, 0.02, and 0.2 mmol/L) of pyruvate and 1 mmol/L dimethyl‐α‐KG (a membrane permeable α‐KG, dm‐α‐KG; Tokyo Chemical Industry Co., Ltd.). Stock solution of dBSA was prepared as previously described . Briefly, BSA was dissolved in distilled water at a concentration of 12%.…”

Section: Methodsmentioning

confidence: 99%

Effects of pyruvate and dimethyl‐α‐ketoglutarate, either alone or in combination, on pre‐ and post‐implantation development of mouse zygotes cultured in vitro

Choi

Kawano

Hiraya

et al. 2019

Reprod Medicine & Biology

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Purpose Dimethyl α‐ketoglutarate (dm‐α‐KG) promotes in vitro development to blastocysts of C57BL/6J X C3He F1 mouse zygotes cultured in medium lacking pyruvate. Here, we examined the effects of pyruvate and dm‐α‐KG on in vitro development to blastocysts of ICR mouse zygotes and their post‐implantation developmental ability. Methods Zygotes were cultured in medium with pyruvate at 0‐0.2 mmol/L in the presence or absence of 1 mmol/L dm‐α‐KG for 96 hours and evaluated for blastocyst formation rates. The resultant blastocysts were non‐surgically transferred to surrogates and evaluated for birth rates. Results In medium lacking pyruvate, zygotes could not develop beyond the two‐cell stage, in the presence or absence of dm‐α‐KG. However, the blastocyst formation rate in medium with 0.01 mmol/L pyruvate (12%) was markedly increased with addition of dm‐α‐KG (49%). Around 80% of embryos developed to blastocysts in medium with 0.2 mmol/L pyruvate, in the presence or absence of dm‐α‐KG. Importantly, birth rate was markedly improved by treatment with 0.2 mmol/L pyruvate and dm‐αKG (31.0%), compared with those with pyruvate treatment alone (16.3%). Conclusions Pyruvate and dm‐α‐KG synergistically work during in vitro culture to markedly improve the blastocyst formation rate and post‐implantation developmental ability of the resultant blastocysts in ICR mice.

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Reprogramming towards totipotency is greatly facilitated by synergistic effects of small molecules

Cited by 31 publications

References 61 publications

Trichostatin A Triggers an Embryogenic Transition in Arabidopsis Explants via an Auxin-Related Pathway

Trichostatin A Triggers an Embryogenic Transition in Arabidopsis Explants via an Auxin-Related Pathway

Peroxiredoxin as a functional endogenous antioxidant enzyme in pronuclei of mouse zygotes

Effects of pyruvate and dimethyl‐α‐ketoglutarate, either alone or in combination, on pre‐ and post‐implantation development of mouse zygotes cultured in vitro

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