Six1 transcription factor an essential regulator in development of embryonic lung epithelial stem cells

Scientists at The Saban Research Institute of Children's Hospital Los Angeles have provided the first evidence that Six1 transcription factor is an essential regulator in the development of embryonic lung epithelial stem cells.

“This finding is clinically relevant since mutations in transcription factors, such as Six1, are associated with specific diseases, and at the same time, they provide therapeutic targets for altering the course of disease progression”

Proper formation and functioning of lung epithelium is essential to life. The self-renewal of embryonic lung stem cells involves a balance between proliferative potential, inhibition of differentiation, and the prevention of senescence or cell death and is crucial for proper lung formation. Perturbation of this balance has been associated with developmental disorders as well as cancer.

Until now, little has been known about the mechanism that controls this balance in embryonic lung epithelial stem cells. David Warburton, MD, DSc, director of Developmental Biology and Regenerative Medicine at The Saban Research Institute, and Ahmed El-Hashash, PhD, senior research scientist carrying out this study, have determined that Six1 transcription factor controls the balance between self-renewal and differentiation and maintains embryonic lung epithelial stem cells. They have also provided the first evidence that Six1 transcription factor coordinates other signaling molecules that are essential for the maintenance of epithelial stem cells in the embryonic lung. Results of this study will be published in the upcoming issue of Developmental Biology.

In vivo and in vitro experiments showed that interfering with Six1 function resulted in severe reduction of epithelial stem cells but increased epithelial differentiation, thereby establishing Six1 as a critical regulator of the balance between stem cell self-renewal and differentiation, cell fate and maintenance of embryonic lung stem cells.

"This finding is clinically relevant since mutations in transcription factors, such as Six1, are associated with specific diseases, and at the same time, they provide therapeutic targets for altering the course of disease progression," said Dr. Warburton.

"Identification of novel Six1 functions in controlling self-renewal and maintaining lung stem cells will likely be instrumental in identifying a cure for congenital lung hypoplasia and bronchopulmonary dysplasia, conditions characterized by a significant deficiency of stem cells. These devastating conditions are, unfortunately, common features of human prematurity and are significant public health issues," said Dr El-Hashash. "These findings may also have an application in the regeneration of lung tissue for restoration of functional alveoli in diseases like chronic obstructive pulmonary disease and fibrosis."

Source Children's Hospital Los Angeles