Studies from Dr. Rongwen Xi's laboratory at NIBS reveal a novel feedback amplification loop between stem cells and their progeny that mediates tissue regeneration and tumorigenesis.

    On May 17, 2016,Dr. Rongwen Xi's group published a research article titled "A feedback amplification loop between stem cells and their progeny promotes tissue regeneration and tumorigenesis" on eLife.

    There are many stem cells in our body responsible for daily maintenance and would healing of many organs. By cell division, adult stem cells can produce progeny cells that, through a process named 'differentiation', become mature cells to replace the old or damaged cells caused by age, injury or diseases. The stem cell division and daughter cell differentiation must be coordinately balanced to meet tissue demand and to maintain tissue homeostasis. Otherwise, tissue degeneration or tumorigenesis may occur. How the stem cell division and daughter cell differentiation are coordinately regulated to meet tissue demand is largely unknown.

    Using fruit fly midgut, a relatively simple model system for epithelial maintenance supported by local stem cells, researchers in Rongwen Xi's laboratory at NIBS find that the intestinal stem cells and their immediate progeny form a regulated feedback amplification loop mediated by a transcription factor Sox21a to control epithelial homeostasis. The amplification loop functions as an efficient way to rapidly generate a large amount of undifferentiated stem cell progeny required for epithelial repair, and its activity is at minimum during regular epithelial homeostasis. Following damage, the amplification loop is transiently activated to promote epithelial regeneration and repair. Strikingly, sustained or irreversible activation of the amplification loop leads to rapid and continuous accumulation of undifferentiated stem cell progeny in the intestine, and consequently tumorigenesis.

    Therefore, this study reveals a novel positive feedback mechanism that promotes epithelial regeneration and tumor development in Drosophila. It would be interesting to determine whether this is a general mechanism underlying tissue regeneration in other tissues, including that in mammals and humans, and whether its dysregulation could be a common cause of cancer.

https://elifesciences.org/content/5/e14330