There and Back Again: Regulation of Stem Cell Homeostasis and Dedifferentiation in the Drosophila Male Germline by me31b

Abstract

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. However, even stem cells can be damaged or lost, leading to a tissue that cannot be properly replenished if stem cells are not replaced or recreated. One method of recreating stem cells is dedifferentiation, the process of a more differentiated/specialized cell reverting back to a stem cell identity. In some cases, dedifferentiation of differentiated/differentiating cells help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is also speculated to underlie tumorigenesis and several previous studies have identified dedifferentiated cells as the source of cancerous growths. Therefore, this process must be tightly controlled. Here, we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance, which is both necessary and sufficient for dedifferentiation. Moreover, our data also reveal new details about nos transcription and translational regulation, a pattern that likely contributes to the gradual rate of differentiation in the spermatogonia. Taken together, our data reveal a method in the testis to balance stem cell maintenance with differentiation: by negatively regulating dedifferentiation while maintaining a gradual pace for differentiation, a pool of differentiating germ cells stands ready for recall as germline stem cells.