Stem cells control tissue regeneration by balancing the ability to create additional stem cells (self-renewal) with the ability to generate daughter cells that differentiate.  Characterizing the local microenvironments, or niches, where stem cells reside is critical to understanding the regulation of stem cells in adult tissues.  We study stem cell regulation in the testis of the fruit fly Drosophila melanogaster.  In this tissue, germline stem cells (GSCs) attach to a cluster of non-dividing somatic cells called the hub.  When a GSC divides, one daughter remains a stem cell, while the other is pushed away from the hub and differentiates into a gonialblast.  Somatic stem cells, called cyst progenitor cells (CPCs), are also attached to the hub.  They produce cyst cells that envelop each gonialblast and support its development.  Each gonialblast divides four times, producing a cluster of spermatogonia that continue to differentiate into sperm.

Both GSCs and CPCs are maintained by the Janus kinase-Signal transducer and activator of transcription (JAK-STAT) signaling pathway.  The hub secretes a ligand (Unpaired) that activates the JAK-STAT pathway in GSCs and CPCs, ensuring that they remain stem cells.  Daughter cells that are pushed away from the hub do not receive enough Unpaired to activate JAK-STAT and instead differentiate.  Differentiation was once thought to be irreversible, but we now know that spermatogonia can reverse their path and de-differentiate into GSCs.  We are investigating the mechanisms that control stem cell maintenance, differentiation, and de-differentiation in the testis.

Selected publications:

M. Issigonis, N. Tulina, M. de Cuevas, C. Brawley, L. Sandler and E. Matunis.  2009.  JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche.  Science 326: 153-156.

M. de Cuevas.  2006.  Drosophila Oogenesis.  In: Encyclopedia of Life Sciences.  John Wiley & Sons Ltd., Chichester.  http://www.els.net/ [doi: 10.1038/npg.els.0001502].