Abstract
<title>Abstract</title> <p>Stem cell–driven tissue development relies on a precise balance between self-renewal and differentiation. In the Drosophila larval wing disc, adult muscle precursors (AMPs) generate the adult flight muscles, yet the mechanisms coordinating intrinsic regulators with epithelial niche signals remain poorly understood. We previously showed that the epigenetic regulator Ten-Eleven Translocation (TET) is required for flight muscle development independently of its catalytic activity. Here, we combined single-cell transcriptomics with genome-wide profiling of TET occupancy and histone modifications to define its role in AMP maintenance. TET loss profoundly remodels the AMPs transcriptional landscape, promoting a premature shift towards differentiation that is accompanied by altered expression of genes implicated in cell proliferation and mitochondrial metabolism. In AMPs, TET directly binds and activates genes required for progenitor maintenance, including the stemness regulator zfh1, thereby preventing differentiation. In parallel, TET functions non-cell autonomously in the epithelial niche, likely through a chromatin-independent mechanism, to promote expression of the Notch ligand Delta. Finally, we identify the zinc-finger transcription factor Jim as a candidate mediator of TET-dependent transcriptional activation in AMPs. Together, our findings reveal complementary cell-autonomous and non-cell autonomous functions of TET that integrate intrinsic transcriptional programs with niche-derived signalling to preserve muscle progenitor identity and coordinate self-renewal and differentiation.</p>