Related Experiment Video
Updated: Sep 3, 2025
11:42
Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
Published on: November 4, 2019
6.1K
SOX9 reprograms endothelial cells by altering the chromatin landscape.
Bettina M Fuglerud1,2,3, Sibyl Drissler1,4, Jeremy Lotto1,4
1Terry Fox Laboratory, BC Cancer, Vancouver, British Columbia V5Z 1L3, Canada.
Nucleic Acids Research
|July 29, 2022
Summary
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.
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.
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