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Related Concept Videos

Overview of Metabolism01:40

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Living cells constantly carry out various chemical reactions which are necessary for their proper functioning. These reactions are interlinked to one another via multiple pathways. The collection of these chemical reactions is known as metabolism.
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Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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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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Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
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Altering metabolism programs cell identity via NAD+-dependent deacetylation.

Robert A Bone1, Molly P Lowndes1,2, Silvia Raineri1

  • 1Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

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|April 25, 2025
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Altering metabolism in embryonic stem cells (ESCs) by replacing glucose with galactose promotes a developmental identity. This shift enhances oxidative phosphorylation (OXPHOS), reprogramming cells for improved function.

Keywords:
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Area of Science:

  • Cell Biology
  • Metabolic Reprogramming
  • Developmental Biology

Background:

  • Cellular metabolism is intrinsically linked to gene regulation.
  • Understanding how metabolic shifts influence cell identity is crucial for developmental biology.
  • Embryonic stem cells (ESCs) possess unique metabolic characteristics that support pluripotency.

Purpose of the Study:

  • To investigate how metabolic alterations can direct cellular identity in ESCs.
  • To explore the role of oxidative phosphorylation (OXPHOS) in reprogramming ESCs towards an inner cell mass (ICM)-like state.
  • To elucidate the molecular mechanisms linking metabolic changes to transcriptional programming.

Main Methods:

  • Culturing ESCs in media with D-galactose instead of D-glucose.
  • Measuring changes in cellular metabolism, focusing on glycolysis and OXPHOS.
  • Analyzing histone and transcription factor acetylation levels.
  • Assessing changes in gene expression and enhancer activity.

Main Results:

  • Replacing D-glucose with D-galactose inhibited glycolysis and stimulated OXPHOS in ESCs.
  • Enhanced OXPHOS activated NAD+-dependent Sirtuin deacetylases.
  • Deacetylation of histones and transcription factors focused enhancer activity and reduced transcriptional noise.
  • This metabolic shift promoted a developmental identity resembling the ICM.

Conclusions:

  • Metabolic reprogramming, specifically enhancing OXPHOS, can induce a specific developmental cell identity in ESCs.
  • The NAD+/NADH coenzyme ratio, modulated by OXPHOS, plays a key role in programming lineage-specific transcription.
  • This mechanism suggests a paradigm for cellular rejuvenation through targeted metabolic and enzymatic activity.