Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06519, USA.
Yale Stem Cell Center, Yale School of Medicine, New Haven, CT 06519, USA; Department of Cell Biology, Yale School of Medicine, New Haven, CT 06519, USA.
Stem Cell Reports. 2023 Feb 14;18(2):503-518. doi: 10.1016/j.stemcr.2023.01.001. Epub 2023 Feb 2.
PIWI genes are well known for their germline but not somatic functions. Here, we report the function of the Drosophila piwi gene in the adult gut, where intestinal stem cells (ISCs) produce enteroendocrine cells and enteroblasts that generate enterocytes. We show that piwi is expressed in ISCs and enteroblasts. Piwi deficiency reduced ISC number, compromised enteroblasts maintenance, and induced apoptosis in enterocytes, but did not affect ISC proliferation and its differentiation to enteroendocrine cells. In addition, deficiency of zygotic but not maternal piwi mildly de-silenced several retrotransposons in the adult gut. Importantly, either piwi mutations or piwi knockdown specifically in ISCs and enteroblasts shortened the Drosophila lifespan, indicating that intestinal piwi contributes to longevity. Finally, our mRNA sequencing data implied that Piwi may achieve its intestinal function by regulating diverse molecular processes involved in metabolism and oxidation-reduction reaction.
PIWI 基因以其生殖系而非体细胞功能而闻名。在这里，我们报告了果蝇 piwi 基因在成年肠道中的功能，在肠道中，肠干细胞 (ISCs) 产生内分泌细胞和肠母细胞，从而产生肠细胞。我们发现 piwi 在 ISCs 和肠母细胞中表达。piwi 缺陷减少了 ISC 的数量，损害了肠母细胞的维持，并诱导肠细胞凋亡，但不影响 ISC 的增殖及其向内分泌细胞的分化。此外，合子而非母体 piwi 的缺陷轻微地使成年肠道中的几个逆转座子去沉默。重要的是，无论是 piwi 突变还是特异性敲低 ISCs 和肠母细胞中的 piwi，都缩短了果蝇的寿命，表明肠道中的 piwi 有助于长寿。最后，我们的 mRNA 测序数据表明，Piwi 可能通过调节涉及代谢和氧化还原反应的多种分子过程来发挥其肠道功能。
