Department of Biology, Indiana University, Bloomington, IN 47405.
Departamento de Genética, Facultad de Ciencies Biológicas and Estructura de Recerca Interdisciplinar en Biotecnologia i Biomedicina, University of Valencia, 46100 Burjasot, Spain.
Proc Natl Acad Sci U S A. 2021 May 25;118(21). doi: 10.1073/pnas.2022583118.
Adult organisms must sense and adapt to environmental fluctuations. In high-turnover tissues such as the intestine, these adaptive responses require rapid changes in gene expression that, in turn, likely involve posttranscriptional gene control. However, intestinal-tissue-specific microRNA (miRNA)-mediated regulatory pathways remain unexplored. Here, we report the role of an intestinal-specific miRNA, , that non-cell autonomously regulates stem cell numbers during tissue homeostasis and regeneration in the adult midgut. We identify its downstream target , the ortholog of mammalian KLF10/11 transcription factors, which mediates this function by promoting paracrine enterocyte-to-stem-cell bone morphogenetic protein (BMP) signaling. We also show that mature levels transiently decrease in response to stress and that this decrease is required for proper stem cell expansion during tissue regeneration. In summary, we have identified a posttranscriptional mechanism that modulates BMP signaling activity within adult intestinal tissue during both normal homeostasis and tissue regeneration to regulate intestinal stem cell numbers.
成年生物必须感知和适应环境波动。在高周转率组织如肠道中，这些适应性反应需要基因表达的快速变化，而这可能涉及转录后基因控制。然而，肠道组织特异性 microRNA（miRNA）介导的调控途径仍未被探索。在这里，我们报告了一种肠道特异性 miRNA， ，它在组织稳态和成年中肠再生过程中通过非细胞自主方式调节干细胞数量。我们确定了它的下游靶标 ，哺乳动物 KLF10/11 转录因子的同源物，它通过促进旁分泌肠细胞-干细胞骨形态发生蛋白（BMP）信号传导来介导这种功能。我们还表明，成熟 的水平在应激下会短暂降低，而这种降低对于组织再生过程中干细胞的适当扩增是必需的。总之，我们已经确定了一种转录后机制，该机制在正常稳态和组织再生期间调节成年肠道组织内的 BMP 信号活性，从而调节肠道干细胞数量。
