Canonical and non-canonical functions of STAT in germline stem cell maintenance

BackgroundMaintenance of the Drosophila male germline stem cells (GSCs) requires activation of the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway by niche signals. The precise role of JAK/STAT signaling in GSC maintenance, however, remains incompletely understood. ResultsHere, we show that, GSC maintenance requires both canonical and non-canonical JAK/STAT signaling, in which unphosphorylated STAT (uSTAT) maintains heterochromatin stability by binding to heterochromatin protein 1 (HP1). We found that GSC-specific overexpressing STAT, or even the transcriptionally inactive mutant STAT, increases GSC number and partially rescues the GSC-loss mutant phenotype due to reduced JAK activity. Furthermore, we found that both HP1 and STAT are transcriptional targets of the canonical JAK/STAT pathway in GSCs, and that GSCs exhibit higher heterochromatin content. ConclusionsThese results suggest that persistent JAK/STAT activation by niche signals leads to the accumulation of HP1 and uSTAT in GSCs, which promote heterochromatin formation important for maintaining GSC identity. Thus, the maintenance of Drosophila GSCs requires both canonical and non-canonical STAT functions within GSCs for heterochromatin regulation.

Automated summary

The maintenance of Drosophila male germline stem cells (GSCs) requires both canonical and non-canonical Janus kinase/signal transducer and activators of transcription (JAK/STAT) signaling. Unphosphorylated STAT (uSTAT) binds to heterochromatin protein 1 (HP1) to stabilize heterochromatin and maintain GSC identity. Persistent activation of JAK/STAT pathway leads to the accumulation of HP1 and uSTAT in GSCs, promoting heterochromatin formation critical for GSC maintenance.