A stem cell with genetic alterations that eliminate JAK-STAT signaling and promote division produces derivatives (green cells), which accumulate as follicle stem cells (center) that form few or no follicle cells (red, right) in the ovary of an adult fruit fly. Image credit: David Melamed (CC BY 4.0)
Adult organisms contain a variety of cells that are routinely replaced using adult stem cells which can generate the cells of a specific tissue. These stem cells are often clustered into small groups, where combinations of chemical signals from nearby cells can encourage each stem cell to divide or ‘differentiate’ into another type of cell. These different signals must somehow balance stem cell division and differentiation to maintain the size and shape of the community.
The ovary of an adult fruit fly contains a group of adult stem cells called follicle stem cells, or FSCs for short. FSCs support the continual production of eggs by supplying two types of cell from opposite faces of the stem cell cluster: dividing follicle cells emerge from the back of the cluster and guide late egg development, while non-dividing escort cells come from the front and guide early egg development. Two of the signals that control FSCs are graded over the cluster. JAK-STAT signaling is strongest in the follicle cell territory and gradually declines towards the front, while Wnt signaling is strongest in escort cells and absent from early follicle cells. However, it was unclear how the gradients of these two signals maintain the FSC population and control the formation of follicle and escort cells.
To answer this question, Melamed and Kalderon used genetic engineering to modify the strength of these two signals. The experiments measured how this affected the rate at which FSCs divide and are converted into follicle or escort cells. Melamed and Kalderon found that the strength of JAK-STAT signaling dictated division rates, which may explain why the rate cells divide varies across the FSC cluster and escort cells do not divide at all. JAK-STAT signaling also stimulated FSCs to become follicle cells and opposed their conversion to escort cells. Conversely, stronger Wnt signaling favored the production of escort cells and inhibited FSCs from transitioning to follicle cells. This suggests that the relative strength of these two opposing signals helps maintain thecorrect number of FSCs while also balancing the formation of follicle and escort cells.
JAK-STAT, Wnt and other signals guide the development of many organisms, including humans, and have also been linked to cancer. Therefore, the principles and mechanisms uncovered may apply to other types of stem cells. Furthermore, this work highlights genetic changes that can allow a mutant stem cell to amplify and take over an entire stem cell community, which may play a role in cancer and other illnesses.
