A population of adult satellite-like cells in <i>Drosophila</i> is maintained through a switch in RNA-isoforms.

Abstract

Adult stem cells are important for tissue maintenance and repair. One key question is how such cells are specified and then protected from differentiation for a prolonged period. Investigating the maintenance of <i>Drosophila</i> muscle progenitors (MPs) we demonstrate that it involves a switch in <i>zfh1/ZEB1</i> RNA-isoforms. Differentiation into functional muscles is accompanied by expression of <i>miR-8/miR-200</i>, which targets the major <i>zfh1-long</i> RNA isoform and decreases Zfh1 protein. Through activity of the Notch pathway, a subset of MPs produce an alternate <i>zfh1-short</i> isoform, which lacks the <i>miR-8</i> seed site. Zfh1 protein is thus maintained in these cells, enabling them to escape differentiation and persist as MPs in the adult. There, like mammalian satellite cells, they contribute to muscle homeostasis. Such preferential regulation of a specific RNA isoform, with differential sensitivity to miRs, is a powerful mechanism for maintaining a population of poised progenitors and may be of widespread significance.