Combinatorial metabolism drives the naive to primed pluripotent chromatin landscape

Ehnes, Devon; Hussein, Abdiasis M.; Ware, Carol B.; Mathieu, Julie; Ruohola‐Baker, Hannele

doi:10.1016/j.yexcr.2020.111913

Cited by 11 publications

(8 citation statements)

References 99 publications

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“…The morula to blastocyst is a very dynamic period in metabolic changes within early in vitro development [ 29 , 30 ]. In parallel to progress in blastulation, the embryo increases glycolytic flux and mitochondrial respiration [ 31 , 32 ] because of strict epigenetic control [ 33 ]. Such major changes are the tip of the iceberg in terms of the metabolic changes that arise when combined with breed, embryonic stage and culture conditions, whose certainly considerable impact has been evaluated in a companion study with UHPLC-MS during the development of morula and blastocysts in SCS [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

et al. 2021

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In vitro produced (IVP) embryos show large metabolic variability induced by breed, culture conditions, embryonic stage and sex and gamete donors. We hypothesized that the birth potential could be accurately predicted by UHPLC-MS/MS in culture medium (CM) with the discrimination of factors inducing metabolic variation. Day-6 embryos were developed in single CM (modified synthetic oviduct fluid) for 24 h and transferred to recipients as fresh (28 ETs) or frozen/thawed (58 ETs) Day-7 blastocysts. Variability was induced with seven bulls, slaughterhouse oocyte donors, culture conditions (serum + Bovine Serum Albumin [BSA] or BSA alone) prior to single culture embryonic stage records (Day-6: morula, early blastocyst, blastocyst; Day-7: expanding blastocyst; fully expanded blastocysts) and cryopreservation. Retained metabolite signals (6111) were analyzed as a function of pregnancy at Day-40, Day-62 and birth in a combinatorial block study with all fixed factors. We identified 34 accumulated metabolites through 511 blocks, 198 for birth, 166 for Day-62 and 147 for Day-40. The relative abundance of metabolites was higher within blocks from non-pregnant (460) than from pregnant (51) embryos. Taxonomy classified lipids (12 fatty acids and derivatives; 224 blocks), amino acids (12) and derivatives (3) (186 blocks), benzenoids (4; 58 blocks), tri-carboxylic acids (2; 41 blocks) and 5-Hydroxy-l-tryptophan (2 blocks). Some metabolites were effective as single biomarkers in 95 blocks (Receiver Operating Characteristic – Area Under the Curve [ROC-AUC]: 0.700–1.000). In contrast, more accurate predictions within the largest data sets were obtained with combinations of 2, 3 and 4 single metabolites in 206 blocks (ROC-AUC = 0.800–1.000). Pregnancy-prone embryos consumed more amino acids and citric acid, and depleted less lipids and cis-aconitic acid. Big metabolic differences between embryos support efficient pregnancy and birth prediction when analyzed in discriminant conditions.

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Section: Introductionmentioning

confidence: 99%

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

et al. 2021

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“…Embryonic diapause is associated with reduced metabolic activities, including pro tein and DNA synthesis and carbohydrate metabolism [1,[14][15][16]. We and others hav shown that pluripotent stem cells grown in vitro in states corresponding to pre-implanta tion (naïve) and post-implantation (primed) stages exhibit different metabolic and epige netic (discussed in 3.3) profiles [17][18][19][20][21]. Naïve pluripotent stem cells are able to perform oxidative phosphorylation, fatty acid oxidation, and glycolysis, while primed cells rely exclusively on glycolysis as a source of energy [17,22].…”

Section: Diapause Metabolismmentioning

confidence: 99%

Molecular Regulators of Embryonic Diapause and Cancer Diapause-like State

Hussein

Balachandar

Mathieu

et al. 2022

Cells

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Embryonic diapause is an enigmatic state of dormancy that interrupts the normally tight connection between developmental stages and time. This reproductive strategy and state of suspended development occurs in mice, bears, roe deer, and over 130 other mammals and favors the survival of newborns. Diapause arrests the embryo at the blastocyst stage, delaying the post-implantation development of the embryo. This months-long quiescence is reversible, in contrast to senescence that occurs in aging stem cells. Recent studies have revealed critical regulators of diapause. These findings are important since defects in the diapause state can cause a lack of regeneration and control of normal growth. Controlling this state may also have therapeutic applications since recent findings suggest that radiation and chemotherapy may lead some cancer cells to a protective diapause-like, reversible state. Interestingly, recent studies have shown the metabolic regulation of epigenetic modifications and the role of microRNAs in embryonic diapause. In this review, we discuss the molecular mechanism of diapause induction.

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“…One of the many intriguing aspects of HIF-1α elevation is the de-differentiation of mature cell populations to an immature state determined by molecular markers and aerobic glycolysis (50)(51)(52)(53)(54)(55)(56)(57).…”

Section: The Role Of Hif-1α and Changes In Vascularizationmentioning

confidence: 99%

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

Zebrowitz

Kajikawa

Bedelbaeva

et al. 2021

Preprint

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Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur.In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement a ligature around the upper second molar which leads to inflammation and bone breakdown and faithfully replicates the bacterially-induced inflammatory etiology of human PD to induce bone degeneration. After 10 days, the ligature is removed and the mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and the regenerative response is completely blocked by siHIF1a. Here, we observe that timed-release 1,4-DPCA rapidly and completely restores bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to stem cell migration into the site and/or de-differentiation of local tissue, PDL cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells.

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Combinatorial metabolism drives the naive to primed pluripotent chromatin landscape

Cited by 11 publications

References 99 publications

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

The Metabolic Signature of In Vitro Produced Bovine Embryos Helps Predict Pregnancy and Birth after Embryo Transfer

Molecular Regulators of Embryonic Diapause and Cancer Diapause-like State

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

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