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Other Glycolytic Pathways01:24

Other Glycolytic Pathways

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The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
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Nearly all the energy used by cells comes from the bonds that make up complex organic compounds. These organic compounds are broken down into simpler molecules, such as glucose. As a result, cells extract energy from glucose over many chemical reactions—a process called cellular respiration.
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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Glucose is the source of nearly all energy used by organisms. The first step of converting glucose into usable energy is called glycolysis. Glycolysis occurs in the cytosol of the cell over two phases: an energy-requiring phase and an energy-releasing phase. Over the first three steps, glucose is converted into different forms and attached to two phosphate groups donated by two ATP molecules, resulting in an unstable sugar. In the next two stages, the unstable sugar splits into two sugar...
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Glycolysis01:23

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BRG1 improves reprogramming efficiency by enhancing glycolytic metabolism.

Xuan Ren1, Shihai Huang2, Jianchun Xu1

  • 1Guangxi Key Laboratory of Animal Breeding and Disease Control, College of Animal Science and Technology, Guangxi University, Nanning, 530005, China.

Cellular and Molecular Life Sciences : CMLS
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BRG1 enhances induced pluripotent stem cell (iPSC) generation in pigs by promoting glycolysis via the PI3K/AKT pathway. This epigenetic regulator boosts pluripotency factor expression and metabolic reprogramming for efficient iPSC production.

Keywords:
BRG1GlycolysisH3K9me3PI3K/AKT signaling pathwayPorcine iPSCsTranscriptional activity

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Area of Science:

  • Stem Cell Biology
  • Epigenetics
  • Metabolic Reprogramming

Background:

  • BRG1 is known to influence induced pluripotent stem cell (iPSC) generation through epigenetic modifications and transcription factor binding.
  • The specific role of BRG1 in cellular metabolism during the reprogramming process remains largely unexplored.

Purpose of the Study:

  • To investigate the role of BRG1 in cellular metabolism during porcine iPSC generation.
  • To elucidate the molecular mechanisms by which BRG1 affects metabolic reprogramming and pluripotency factor expression.

Main Methods:

  • Assessed the efficiency of porcine iPSC generation with varying BRG1 levels.
  • Analyzed cellular glycolysis and related metabolites.
  • Examined the transcriptional activity of glycolysis-related genes (HK2, PKM2, PFK-1) and H3K9me3 enrichment.
  • Investigated the PI3K/AKT signaling pathway using inhibitors (LY294002) and assessed the effects of glycolysis inhibitors (2-DG) and a BRG1 inhibitor (PFI-3).

Main Results:

  • BRG1 overexpression improved porcine iPSC generation efficiency and upregulated pluripotency factors.
  • BRG1 promoted cellular glycolysis and increased glycolysis-related metabolites.
  • BRG1 enhanced the transcriptional activity of glycolysis genes and reduced H3K9me3 enrichment at target gene promoters.
  • BRG1 increased AKT phosphorylation; PI3K/AKT pathway inhibition impaired iPSC generation and glycolysis, effects rescued by BRG1 overexpression. Glycolysis and BRG1 inhibitors showed similar effects.

Conclusions:

  • BRG1 facilitates porcine iPSC generation by promoting glycolytic reprogramming.
  • The PI3K/AKT signaling pathway is crucial for BRG1-mediated metabolic reprogramming and pluripotency.
  • BRG1 acts as a key regulator linking epigenetic modifications, cellular metabolism, and pluripotency during iPSC generation.