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Related Concept Videos

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Chromatin Modification in iPS Cells

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
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Probing for Mitochondrial Complex Activity in Human Embryonic Stem Cells
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Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model.

Sepideh Mostafavi1, Novin Balafkan1,2,3, Ina Katrine Nitschke Pettersen4

  • 1Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Frontiers in Cell and Developmental Biology
|November 1, 2021
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Mitochondrial remodeling during stem cell differentiation is crucial for cell fate. This study shows mitochondrial content decreases during mesoderm differentiation, contrary to expectations, highlighting lineage-specific metabolic adaptations.

Keywords:
OXPHOScardiomyocytedevelopmentmetabolismmitochondriastem cells

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Metabolic Regulation

Background:

  • Stem cell pluripotency and differentiation are regulated by metabolic shifts, particularly from glycolysis to oxidative phosphorylation (OXPHOS).
  • The metabolic switch during germ layer specification is thought to be lineage-specific, with differing roles of glycolysis and OXPHOS.
  • Understanding mitochondrial adaptation during differentiation is key to stem cell applications.

Purpose of the Study:

  • To investigate mitochondrial remodeling and adaptation during human pluripotent stem cell differentiation into mesodermal lineages, specifically cardiac progenitors and cardiomyocytes.
  • To clarify the relationship between mitochondrial content, activity, and respiration during mesodermal differentiation.

Main Methods:

  • Human pluripotent stem cells were differentiated into cardiac progenitors and cardiomyocytes.
  • Mitochondrial content, activity, and oxidative phosphorylation (OXPHOS) capacity were assessed throughout the differentiation process.

Main Results:

  • Mitochondrial content progressively decreased during mesoderm differentiation into cardiac cells.
  • Despite reduced mitochondrial content, mitochondrial activity and ATP-linked respiration increased.
  • This contrasts with findings in neuronal differentiation, indicating lineage-specific mitochondrial remodeling.

Conclusions:

  • Mitochondrial remodeling during the transition from pluripotent to multipotent states shows similarities across ectodermal and mesodermal lineages.
  • Further differentiation into specific cell types involves distinct, cell-lineage-specific mitochondrial adaptations.
  • Increased OXPHOS activity during differentiation does not necessitate an increase in mitochondrial content.