poly-A RNA profiling of Drosophila neural stem cells (type I NBs) and GMCs of different ages reveal genes involved in cell fate stabilization

Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+–ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways. Overall design: Comparison of transcriptomes of wild-type type I NBs and GMCs of different ages (1.5h, 3h or 5h old) isolated by FACS from Drosophila melanogaster larval brains.

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Wissel S, Harzer H, Bonnay F, Burkard TR, Neumüller RA, Knoblich JA