A feedforward loop between JAK/STAT downstream target p115 and STAT in germline stem cells

Area of Science:

• Developmental Biology
• Cell Biology
• Stem Cell Biology

Background:

• Germline stem cells (GSCs) are crucial for tissue homeostasis.
• Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling is known to maintain GSC fate in Drosophila testes.
• The precise downstream mechanisms by which JAK/STAT signaling regulates male GSC fate are not fully understood.

Purpose of the Study:

• To identify downstream targets of JAK/STAT signaling involved in maintaining male GSC fate.
• To elucidate the role of the identified target in GSC maintenance and its relationship with JAK/STAT signaling.

Main Methods:

• Identification of p115 as a putative downstream target of JAK/STAT signaling.
• Analysis of p115 localization and function in germline cells using microscopy and depletion studies.
• Investigation of the interaction between p115 and STAT, and the effect of p115 depletion on STAT stability.
• Assessment of GSC loss and restoration through ectopic STAT expression.

Main Results:

• p115, a tER/cis-Golgi golgin protein, was identified as a downstream target of JAK/STAT signaling.
• p115 is localized in the cytosol, ER, and Golgi apparatus, and is essential for their morphology.
• Depletion of p115 in GSCs leads to aberrant spindle orientation and GSC loss.
• p115 directly associates with and stabilizes STAT, and ectopic STAT expression rescues GSC loss.

Conclusions:

• JAK/STAT signaling and p115 form a feedforward loop to maintain male GSC fate.
• p115 plays a critical role in GSC maintenance by stabilizing STAT and ensuring proper cell morphology and division.
• This study provides novel insights into the regulatory mechanisms controlling stem cell maintenance via JAK/STAT signaling.