Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard-Karls-University of Tübingen, Tübingen, Germany.
Cell Rep. 2020 Mar 3;30(9):3183-3194.e4. doi: 10.1016/j.celrep.2020.02.020.
Biofluids contain various circulating cell-free RNAs (ccfRNAs). The composition of these ccfRNAs varies among biofluids. They constitute tantalizing biomarker candidates for several pathologies and have been demonstrated to be mediators of cellular communication. Little is known about their function in physiological and developmental settings, and most works are limited to in vitro studies. Here, we develop iTAG-RNA, a method for the unbiased tagging of RNA transcripts in mice in vivo. We use iTAG-RNA to isolate hepatocytes and kidney proximal epithelial cell-specific transcriptional responses to a dietary challenge without interfering with the tissue architecture and to identify multiple hepatocyte-secreted ccfRNAs in plasma. We also identify specific transfer of liver-derived ccfRNAs to adipose tissue and skeletal muscle, where they likely constitute a buffering system to maintain lipid homeostasis under acute high-fat-diet feeding. Our findings directly demonstrate in vivo transfer of RNAs between tissues and highlight its implications for endocrine signaling and homeostasis.
生物体液中包含各种循环的无细胞 RNA（ccfRNA）。这些 ccfRNA 在不同的生物体液中的组成有所不同。它们是多种病理的有前途的生物标志物候选物，并已被证明是细胞通讯的介质。人们对它们在生理和发育环境中的功能知之甚少，而且大多数研究都仅限于体外研究。在这里，我们开发了 iTAG-RNA，这是一种在体内对小鼠的 RNA 转录物进行无偏标记的方法。我们使用 iTAG-RNA 来分离肝细胞和肾脏近端上皮细胞对饮食挑战的特定转录反应，而不会干扰组织结构，并鉴定出多种在血浆中分泌的肝细胞 ccfRNA。我们还鉴定了特定的肝脏衍生的 ccfRNA 向脂肪组织和骨骼肌的转移，它们可能构成了在急性高脂肪饮食喂养下维持脂质动态平衡的缓冲系统。我们的研究结果直接证明了组织间 RNA 的体内转移，并强调了其对内分泌信号和动态平衡的影响。
