Stem cells are fundamental for tissue formation in all multicellular organisms. In all organs and tissues, stem cells are supported by the surrounding cellular microenvironment, or ‘niche’, which ensures renewal and differentiation through physical interactions with the extracellular matrix (ECM) and cell signalling. Yet, despite the critical role of the niche in stem cell fate control we know relatively little of the molecular mechanisms controlling stem cell-niche communication in mammalian systems, in part, due a deficiency of models for investigating these interactions in vivo. In contrast, the Drosophila ovary, where the importance of interactions between the germline stem cells (GSCs) and somatic niche was first identified, provides an in vivo system for genetic manipulation of the niche and molecular and cellular analysis of the stem cell compartment in vivo.
Here we demonstrate depletion of the single-stranded DNA/RNA binding protein, Half-pint (Hfp), in the GSC niche is sufficient to generate a niche ectopic to the GSC compartment. Although we previously characterised Hfp as a negative transcriptional repressor of Myc in the wing, co-knockdown of Myc did not modify the ectopic niche phenotype. Thus, we used Targeted-DamID to profile genome wide Hfp binding specifically in the ovarian niche. Significant Hfp enrichment was detected on 2572 genes and, consistent with targets regulating stem cell niche communication, gene ontology analysis identified core ECM factors, including basement membrane proteins, collagen IV and laminin subunits. Thus, we are investigating the hypothesis that loss of Hfp function enables formation of an ectopic niche, capable of GSC renewal and differentiation, through dysregulation of the ECM.