Single‐cell transcriptome analysis reveals that maternal obesity affects DNA repair, histone methylation, and autophagy level in mouse embryos

Pan, Meng-Hao; Zhu, Chengcheng; Ju, Jia-Qian; Xu, Yuping; Luo, Shi‐Ming; Sun, Shao‐Chen; Ou, Xiang‐Hong

doi:10.1002/jcp.30201

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Obese mice fed an HFD showed a variety of defects in oocytes that influenced the offspring’s tendency to develop metabolic disease. The expression of the autophagy-related gene Rraga was reduced in obese mice [ 17 ]. Cd36 , which belongs to the class B scavenger receptors, is involved in various diseases and conditions, such as insulin resistance, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD) [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq analysis of obese Pdha1fl/flLyz2-Cre mice induced by a high-fat diet

Geng

Yuan

He³

et al. 2023

Exp. Anim.

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Pyruvate dehydrogenase complex (PDH) is an important complex of three enzymes that transforms pyruvate into acetyl-CoA, subsequently entering the tricarboxylic acid (TCA) cycle to produce ATP and electron donors. As a key regulator of energy and metabolic homeostasis, PDH is considered a potential therapeutic target of many diseases. On the other hand, the relationship between PDH and obesity is not clear. In this study, peripheral blood of Pdha1 fl/fl Lyz2-Cre and C57BL/6 mice fed a high-fat diet (HFD) was collected and subjected to extensive transcriptome sequencing.Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathways analyses were performed based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the genes selected from RNA sequencing (RNA-seq). Eventually, we found that Pdha1 fl/fl Lyz2-Cre mice were more susceptible to HFD-induced obesity. A total of 302 up-regulated genes and 30 downregulated genes were screened that were differentially expressed between Pdha1 fl/fl Lyz2-Cre mice fed the HFD and the control groups. Furthermore, we verified that significant transcriptional changes in the genes Sgstm1,

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Section: Discussionmentioning

confidence: 99%

RNA-Seq analysis of obese Pdha1fl/flLyz2-Cre mice induced by a high-fat diet

Geng

Yuan

He³

et al. 2023

Exp. Anim.

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“…The stress-responsive gene HSPA1L was also down-regulated in the SDF1-treated oocytes [ 41 ]. TEX15 , a DNA damage repair gene activated in response to oxidative stress [ 42 , 43 ], was upregulated in the SDF1-treated versus the control oocytes.…”

Section: Discussionmentioning

confidence: 99%

Supplementation of SDF1 during Pig Oocyte In Vitro Maturation Improves Subsequent Embryo Development

et al. 2022

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The quality of in vitro matured oocytes is inferior to that of in vivo matured oocytes, which translates to low developmental capacity of embryos derived from in vitro matured oocytes. The developmental potential of in vitro matured oocytes is usually impaired due to oxidative stress. Stromal cell-derived factor-l (SDF1) can reduce oxidative stress and inhibit apoptosis. The aim of this study was to investigate the effects of SDF1 supplementation during pig oocyte in vitro maturation (IVM) on subsequent embryo development, and to explore the acting mechanisms of SDF1 in pig oocytes. We found that the IVM medium containing 20 ng/mL SDF1 improved the maturation rate of pig oocytes, as well as the cleavage rate and blastocyst rate of embryos generated by somatic cell nuclear transfer, in vitro fertilization, and parthenogenesis. Supplementation of 20 ng/mL SDF1 during IVM decreased the ROS level, increased the mitochondrial membrane potential, and altered the expression of apoptosis-related genes in the pig oocytes. The porcine oocyte transcriptomic data showed that SDF1 addition during IVM altered the expression of genes enriched in the purine metabolism and TNF signaling pathways. SDF1 supplementation during pig oocyte IVM also upregulated the mRNA and protein levels of YY1 and TET1, two critical factors for oocyte development. In conclusion, supplementation of SDF1 during pig oocyte IVM reduces oxidative stress, changes expression of genes involved in regulating apoptosis and oocyte growth, and enhances the ability of in vitro matured pig oocytes to support subsequent embryo development. Our findings provide a theoretical basis and a new method for improving the developmental potential of pig in vitro matured oocytes.

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“…It has also been shown that obesity and the alteration of genes related to fat metabolism are important negative regulators of histone methylation and autophagic processes, as demonstrated by Pan et al with single-cell RNA transcriptome sequencing in mouse embryos [60]. Additionally, this approach further revealed how specific inflammatoryrelated genes are also altered in the oocytes of obese women compared to those with normal body weight [61], suggesting the useful contribution of scRNA-seq in the exploration of complex biological systems such as the immune system.…”

Section: Single-cell Technology Approaches To the Study Of Neurodegenerative Metabolic And Multifactorial Diseasesmentioning

confidence: 94%

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

Leo

Romano

2021

IJMS

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Epigenetic regulators play a crucial role in establishing and maintaining gene expression states. To date, the main efforts to study cellular heterogeneity have focused on elucidating the variable nature of the chromatin landscape. Specific chromatin organisation is fundamental for normal organogenesis and developmental homeostasis and can be affected by different environmental factors. The latter can lead to detrimental alterations in gene transcription, as well as pathological conditions such as cancer. Epigenetic marks regulate the transcriptional output of cells. Centromeres are chromosome structures that are epigenetically regulated and are crucial for accurate segregation. The advent of single-cell epigenetic profiling has provided finer analytical resolution, exposing the intrinsic peculiarities of different cells within an apparently homogenous population. In this review, we discuss recent advances in methodologies applied to epigenetics, such as CUT&RUN and CUT&TAG. Then, we compare standard and emerging single-cell techniques and their relevance for investigating human diseases. Finally, we describe emerging methodologies that investigate centromeric chromatin specification and neocentromere formation.

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Single‐cell transcriptome analysis reveals that maternal obesity affects DNA repair, histone methylation, and autophagy level in mouse embryos

Cited by 9 publications

References 39 publications

RNA-Seq analysis of obese <i>Pdha1<sup>fl/fl</sup></i>Lyz2-Cre mice induced by a high-fat diet

RNA-Seq analysis of obese <i>Pdha1<sup>fl/fl</sup></i>Lyz2-Cre mice induced by a high-fat diet

Supplementation of SDF1 during Pig Oocyte In Vitro Maturation Improves Subsequent Embryo Development

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

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