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Updated: Sep 3, 2025

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SOX9 reprograms endothelial cells by altering the chromatin landscape.

Bettina M Fuglerud1,2,3, Sibyl Drissler1,4, Jeremy Lotto1,4

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|July 29, 2022
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SOX9 acts as a pioneer transcription factor, initiating endothelial-to-mesenchymal transition (EndMT) by altering chromatin structure. This process is crucial in development and diseases like atherosclerosis.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Endothelial-to-mesenchymal transition (EndMT) is a critical process in embryonic development and disease.
  • The transcription factor SOX9 is activated during EndMT, but its precise regulatory roles remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which SOX9 regulates EndMT.
  • To investigate SOX9's function as a transcription factor in controlling cell fate transitions.

Main Methods:

  • Utilized human umbilical vein endothelial cells (HUVECs) as a model for EndMT.
  • Performed genome-wide chromatin landscape mapping to analyze SOX9 binding and its effects.
  • Employed single-cell chromatin accessibility assays to study SOX9 in vivo.

Main Results:

  • SOX9 expression alone is sufficient to induce mesenchymal gene activation and drive endothelial cells towards a mesenchymal fate.
  • SOX9 functions as a pioneer transcription factor, opening chromatin and establishing active histone marks.
  • SOX9 binding is transient, but its effects on chromatin and cell fate are persistent, and it drives EndMT in atherosclerotic lesions.

Conclusions:

  • SOX9 is a key driver of EndMT, acting as a pioneer transcription factor that persistently alters the chromatin landscape.
  • Understanding SOX9's role provides crucial insights into developmental processes and the pathogenesis of human diseases such as atherosclerosis.