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Nox4 promotes endothelial differentiation through chromatin remodeling
F Hahner1, F Moll1, T Warwick1
1Institute for Cardiovascular Physiology, Goethe University, Frankfurt, Germany; German Center of Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt, Germany.
Redox Biology
|July 10, 2022
Summary
Nox4 is crucial for stem cell differentiation into endothelial cells. Its absence delays differentiation and reduces the stability of endothelial cells by affecting histone methylation.
Area of Science:
- Cell Biology
- Biochemistry
- Developmental Biology
Background:
- Nox4, a NADPH oxidase, produces hydrogen peroxide (H2O2), essential for cell homeostasis and differentiation.
- Endothelial cells highly express Nox4, while stem cells have low expression and H2O2 levels.
- Nox4 is hypothesized to be a key factor in endothelial differentiation and homeostasis.
Purpose of the Study:
- To investigate the role of Nox4 in the differentiation of murine inducible pluripotent stem cells (miPSCs) into endothelial cells (ECs).
Main Methods:
- Murine iPSCs from wildtype and Nox4-/- fibroblasts were differentiated into ECs using BMP4 and VEGF.
- Nox4 expression levels were monitored during differentiation.
- The impact of Nox4 deficiency on pluripotency and endothelial markers was assessed.
- Angiogenic capacity and phenotype stability of resulting iPSC-ECs were evaluated.
- The mechanism involving JmjD3 and histone methylation was investigated.
Main Results:
- Nox4 expression increased during miPSC differentiation into ECs.
- Nox4 knockout prolonged pluripotency markers and delayed endothelial marker expression.
- The angiogenic capacity and stability of iPSC-ECs were reduced in Nox4-deficient cells.
- Nox4 deficiency led to lower nuclear JmjD3 and increased H3K27me3, a repressive histone mark.
Conclusions:
- Nox4 promotes miPSC differentiation into ECs.
- Nox4 facilitates endothelial differentiation and stability through JmjD3 oxidation and H3K27me3 demethylation.
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