News Release

Individual variation in buffalo somatic cell cloning efficiency is related to glycolytic metabolism and chromatin structure

Peer-Reviewed Publication

Science China Press

Model of transforming low cloning efficiency buffalo fetal fibroblasts (BFFs) to high cloning efficiency BFFs

image: On the left, the high cloning efficiency buffalo fetal fibroblasts (BFFs) displayed high H3K9 acetylation, low H3K9 methylation companying with low heterochromatin protein 1α (HP1α) expression, and robust glycolysis metabolism. On the right are low cloning efficiency BFFs, which chromatin state and metabolic characteristics are the opposite of the cells with high cloning efficiency. Regulating the metabolic pathway of buffalo fibroblasts with low cloning efficiency to glycolysis, the chromatin state of the cells can be shift to a chromatin state with high cloning efficiency. view more 

Credit: ©Science China Press

Individual variation in fertility, growth and behavior characteristics is a common phenomenon observed in mammals. Among these individual variations, fertility variation attracts more people attention as it concerns with animal reproduction and species continuation. Fertility variation mainly displays as semen variation in fertilization ability and cell variation in efficiency of nuclear transfer (cloning). The individual variation in semen fertilization ability is easy to be understood as it can be linked to the sperm motility variation. However, the individual variation in somatic cell cloning efficiency is hardly to be linked with the visual phenotype of cells. Therefore, Prof. Deshun Shi’s group from State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, is concentrating on this scientific question and a series of deep investigation was performed. They found that buffalo fetal fibroblasts (BFFs) from different individuals differed in their cloning efficiency, chromatin status, epigenetic modifications and glycolytic metabolism. BFFs with high cloning efficiency displayed robust energy metabolism, looser chromatin structure, low expression of heterochromatin protein 1α (HP1α) and high acetylation of H3K9. More regions enriched with H3K9ac were found in BFFs with high cloning efficiency and these differential H3K9ac modification sites were mainly located in the region near to the upstream of genes related to the glycolytic metabolism by ChIP-sequencing analysis. Stronger enrichment signals, especially in critical genes related to glycolysis was also found in BFFs with high cloning efficiency by ATAC-seq profiling. Treatment of low cloning efficiency BFFs with PS48 (an inducer of glycolytic metabolic pathway) could result in a decrease in apoptosis rate, histone deacetylase activity and HP1α expression, increase in the intracellular lactate production, H3K9 acetylation and cloning efficiency. They well linked somatic cell cloning efficiency, chromatin openness, histone acetylation and glycolysis together, and confirmed that the individual variation in somatic cell cloning efficiency can be regulated by altering glycolytic metabolism. Not only their works will enhance the understanding of somatic cell reprogramming mechanism, but also provide a new route to improving the cloning efficiency. These works will be published in Science China-Life Sciences recently.

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