Hmgcr regulates spermatogonial dedifferentiation in Drosophila male germline. CY Ason Chiang¹, Yukiko Yamashita^1,2. 1) Cell and Developmental Biology, University of Michigan, Ann Arbor, MI; 2) Life Sciences Institute, University of Michigan, Ann Arbor, MI.

   Adult stem cell populations sustain highly differentiated but short-lived cells, such as intestinal epithelial cells and sperm. Dedifferentiation, the reversion of differentiated cells into stem cells, is a mechanism to maintain stem cell number, counteracting sporadic loss of stem cells. In spite of its fundamental importance in stem cell maintenance, the mechanisms that regulate dedifferentiation are poorly understood. In Drosophila testes, it has been shown that adult male germline stem cells (GSCs) are maintained at least in part by dedifferentiation. Previously, partially differentiated spermatogonia are shown to be able to migrate back to the stem cell niche to re-acquire stem cell identity. (Sheng and Matunis, (2011) Development.) Recently, we found that Hmgcr, which is known to direct primordial germ cell (PGC) migration during embryogenesis, is expressed in niche cells of adult testes and is required for dedifferentiation. Its expression is up-regulated in GSC niche upon X-ray irradiation, which leads to GSC loss and subsequent dedifferentiation. Our work illuminates an intriguing similarity between the migration of PGCs toward gonadal somatic cells in the embryo and the migration of spermatogonia toward the stem cell niche during dedifferentiation. Furthermore, we found that protein prenylation enzymes downstream of the Hmgcr pathway are also required for dedifferentiation against stem cell loss during aging. Our findings reveal the role of Hmgcr in GSC maintenance in adult testes, and similarity between PGC and GSC specification.