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Transcriptome analysis of high glucose loaded mouse embryo at 2-cell stage treated with ZGW

ABSTRACT: Purpose: Zuo-Gui-Wan (ZGW) is a classic formula in Traditional Chinese Medicine (TCM). Previous studies have shown that it is not only beneficial for Impaired Glucose Tolerance (IGT) of adults but also the offspring. This study is in order to understand the molecular mechanisms of the efficacy of ZGW on IGT. Methods: We used high glucose loaded 2-cell stage mouse embryos as a model, and took advantage of single-cell RNA sequencing technology to analyze the transcriptome of the model with or without ZGW. Results and Conclusions: Results showed that high glucose can down-regulate genes in the ribosome pathway while ZGW can reverse this inhibition and as a result promote the development of embryos loaded with high glucose. We found that high glucose can affect sugar metabolism and influence mitochondrial function, but that ZGW can promote sugar metabolism via the tricarboxylic acid cycle mainly through up-regulating the genes in the respiratory chain and oxidative phosphorylation. The regulation of mitochondrial energy metabolism is the main effect of ZGW on high glucose loaded embryos. Significance: This research not only revealed the global gene regulation changes of high glucose affecting 2-cell stage embryos, but also provided insight on the potential molecular mechanisms of ZGW on the IGT model.

ORGANISM(S): Mus musculus

PROVIDER: GSE85477 | GEO | 2018/07/19

REPOSITORIES: GEO

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Project description:The number of circulating endothelial progenitor cells (EPCs) predicts future development of atherosclerotic cardiovascular disease (ASCVD) and is reduced in patients with type 2 diabetes (T2DM) or impaired glucose tolerance (IGT). Recent studies revealed the contribution of tight control of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as well as fatty acid oxidation in the regulation of stem cell behavior. In this study, we show that how dysregulated glucose and triglyceride metabolism in T2DM/IGT affects the homeostasis of EPCs, i.e. bone marrow stem/progenitor cells (BMSCs). In our clinical study, consistent with previous reports, the patients with IGT or T2DM showed reduced level of circulating EPCs, as compared normal glucose tolerance. On the other hand, fasting or postprandial hypertriglyceridemia (hTG) itself did not affect the level of circulating EPCs. However, further analysis using single and multiple regression analyses strongly suggested that, in the presence of postprandial hTG, postprandial hyperglycemia exerts devastating effect on EPC homeostasis. We therefore carried out the proof of concept study in mice. Our experimental study revealed that repetitive glucose+lipid (G+L) spikes, but not repetitive glucose (G) spikes or lipid (L) spikes, rapidly upregulated p53 in BMSCs and induced premature aging phenotype of bone marrow cells, i.e. the impairment of BMSC quiescence and function, and myeloid-biased differentiation. Subsequent analysis implicated that p53-mediated augmentation of mitochondrial OXPHOS plays pivotal role for the impairment of BMSC quiescence and function. On the other hand, it is still not clear how repetitive G+L injection induced myeloid-biased differentiation. Because cell-fate decisions are executed by transcription factors in response to extracellular signals, and the best-known function of p53 is as a transcription factor, we asked to what extent repetitive glucose spikes and repetitive glucose+TG spikes affect transcriptional regulation in LSK cells.

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Transcriptome analysis of high glucose loaded mouse embryo at 2-cell stage treated with ZGW

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