Background:
Cardiac fibrosis is a lethal outcome of excessive formation of myofibroblasts that are scar-forming cells accumulated after heart injury. It has been reported that cardiac endothelial cells (ECs) contribute to a substantial portion of myofibroblasts through EndoMT. Recent lineage tracing studies demonstrate that myofibroblasts are derived from expansion of resident fibroblasts rather than from transdifferentiation of ECs. However, it remains unknown whether ECs can transdifferentiate into myofibroblasts reversibly or EndoMT genes were just transiently activated in ECs during cardiac fibrosis.
Methods:
By using the dual recombination technology based on Cre-loxP and Dre-rox, we generated a genetic lineage tracing system for tracking EndoMT in cardiac ECs. We used it to examine if there is transiently activated mesenchymal gene expression in ECs during cardiac fibrosis. Activation of the broadly used marker gene in myofibroblasts, αSMA, and the transcription factor that induces epithelial to mesenchymal transition (EMT), Zeb1, was examined.
Results:
The genetic system enables continuous tracing of transcriptional activity of targeted genes
in vivo
. Our genetic fate mapping results revealed that a subset of cardiac ECs transiently expressed
αSMA
and
Zeb1
during embryonic valve formation and transdifferentiated into mesenchymal cells through EndoMT. Nonetheless, they did not contribute to myofibroblasts; nor transiently expressed
αSMA
or
Zeb1
after heart injury. Instead, expression of
αSMA
was activated in resident fibroblasts during cardiac fibrosis.
Conclusions:
Mesenchymal gene expression is activated in cardiac ECs through EndoMT in the developing heart; but ECs do not transdifferentiate into myofibroblasts, nor transiently express some known mesenchymal genes during homeostasis and fibrosis in the adult heart. Resident fibroblasts that are converted to myofibroblasts by activating mesenchymal gene expression are the major contributors to cardiac fibrosis.
Abstract. The literature shows that task conflict plays an important role in the team operation process, but little is known about who exhibits greater creativity when in conflict, leading the team toward greater creativity. To enhance understanding of employee creativity, this study proposed that task conflict has a curvilinear relationship with employee creativity and that employees’ growth need strength moderates the relationship. A cross-level investigation of employee creativity within 59 groups of employees from multiple Chinese companies was conducted. The results showed that task conflict has an inverted U-shaped relationship with employee creativity. Growth need strength was found to have a moderating effect on the relation between task conflict and employee creativity. Theoretical and practical implications were discussed.
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