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Related Concept Videos

Cell Specific Gene Expression01:58

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Updated: Mar 9, 2026

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Cell-specific gene expression plasticity in response to hypoxia promotes high-altitude adaptive evolution.

Wen-Tian Wei1, Ze Yan1, Hui Wu1

  • 1Frontiers Science Center for Molecular Design Breeding (MOE); State Key Laboratory of Animal Biotech Breeding; College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.

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Genetic adaptation reverses cell-specific gene expression plasticity, with immune cells driving adaptation. This study reveals hypoxia adaptation mechanisms and disease insights.

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cellular mechanismexpression plasticitygenetic adaptationhigh-altitude hypoxiasc/snRNA-seq

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Physiology

Background:

  • The interplay between phenotypic plasticity and genetic adaptation is a key evolutionary question.
  • Molecular mechanisms linking plasticity and adaptation, especially during environmental change like hypoxia, remain underexplored.
  • Sheep were used as a model organism to investigate cellular responses to hypoxia.

Purpose of the Study:

  • To explore cell-specific gene expression plasticity and its reversal by genetic adaptation.
  • To identify molecular networks and cellular changes involved in hypoxia acclimatization.
  • To investigate the role of cellular plasticity in hypoxia-related diseases.

Main Methods:

  • Conducted a plain-to-plateau animal translocation experiment with sheep.
  • Generated 27 scRNA-seq and 54 snRNA-seq datasets from brain, heart, and lung tissues.
  • Analyzed gene expression in over 236,000 cells and 900,000 nuclei.

Main Results:

  • Revealed cell-specific gene expression plasticity that is largely reversed by genetic adaptation.
  • Identified immune cells as having high reversing plasticity, promoting adaptation through selection.
  • Discovered a common regulatory network (AP-1→HIF∣-BHLHE41) underlying cellular plasticity in response to hypoxia.
  • Observed cell plasticity, including microglial activation and endothelial-to-mesenchymal transition, across organs.

Conclusions:

  • Cellular expression plasticity is a key feature of hypoxia acclimatization, driven by specific regulatory networks.
  • Immune cell plasticity plays a crucial role in facilitating genetic adaptation to environmental stressors.
  • Understanding cellular responses to hypoxia provides insights into the incidence and progression of related diseases.