A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms.
A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms.
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作者：
Boukhatmi H;Bray S
成体干细胞对组织的维持和修复非常重要。一个关键的问题是，这些细胞是如何被指定的，然后在很长一段时间内免受分化的保护。研究果蝇肌肉祖细胞（MPs）的维持，我们证明它涉及zfh1/ZEB1 rna -亚型的开关。向功能性肌肉的分化伴随着miR-8/miR-200的表达，miR-8/miR-200靶向主要的Zfh1 -long RNA亚型并降低Zfh1蛋白。通过Notch通路的活性，MPs的一个子集产生替代的zfh1-短异构体，缺乏miR-8种子位点。因此，Zfh1蛋白在这些细胞中得以维持，使它们能够避免分化，并在成体中作为MPs持续存在。在那里，像哺乳动物的卫星细胞一样，它们有助于肌肉的内稳态。这种对特定RNA异构体的优先调控，对mir具有不同的敏感性，是维持稳定的祖细胞群体的强大机制，可能具有广泛的意义。
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 Drosophila muscle progenitors (MPs) we demonstrate that it involves a switch in zfh1/ZEB1 RNA-isoforms. Differentiation into functional muscles is accompanied by expression of miR-8/miR-200, which targets the major zfh1-long RNA isoform and decreases Zfh1 protein. Through activity of the Notch pathway, a subset of MPs produce an alternate zfh1-short isoform, which lacks the miR-8 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.