Stem cell self-renewal and differentiation are complex processes that require stem cells to maintain their identity and also respond to changes within their microenvironment, the stem cell niche. Mutations that affect the genetic composition of the stem cell pool can drastically change how niche signals are sent and received. This in turn alters the cellular composition of the stem cell niche and consequently the genetic composition of the tissue. Such changes include mutations to a cells' sex identity. Although cellular sex identity was thought to be established during development, recent studies have shown that this process is actually strictly maintained throughout adulthood. Changes to cellular sex identity can strongly impact not only the stem cell niche, but also the overall composition of the tissue leading to aberrant tissue function. The goal of this proposal is to identify the molecular mechanisms that modulate stem cell maintenance versus cellular sex identity throughout adulthood. Recently, the Jak/STAT signaling effector and stem cell regulator chinmo was identified to also actively maintain the sex identity of somatic stem cells in the adult Drosophila testis, preventing the feminization of these cells and thus the overall tissue. Overexpressing the canonical sex determination factor DsxM in somatic stem cells that have lost chinmo results in a partial rescue of the sex transformation phenotype, suggesting that chinmo has other targets in addition to DsxM. To determine the downstream targets of chinmo, a novel technique called targeted DNA Adenine Methyltransferase Identification will be used to identify genes that contribute to both stem cell identity and cellular sex maintenance of stem cells in the adult Drosophila testis and ovary. By uncovering how stem cell fate and cellular sex identity are regulated in adult stem cell niches, we can better understand the mechanisms necessary to promote normal tissue homeostasis.
The Jak/STAT signaling effector chinmo has been identified as a gene that plays a critical role in both stem cell fate and cellular sex identity maintenance in stem cells of adult tissues. Uncovering the downstream targets of chinmo will provide better insight into the mechanisms that modulate maintenance versus sex identity throughout adulthood.
