In-vivo targeted tagging of RNA isolates cell specific transcriptional responses to environmental stimuli and identifies liver-to-adipose RNA transfer

J. Darr; M. Lassi; Archana Tomar; R. Gerlini; F. Scheid; M. Hrabe de Angelis; M. Witting; R. Teperino

To assess the feasibility of detecting dynamic transcriptional responses using iTag-RNA, we Table 7) . 294 As opposed to liver, diet-induced differential expression in the kidney was limited to 108 Taken together, these results provide a proof-of-concept that iTAG-RNA allows isolation of cell-300 type specific transcriptional responses to environmental challenges. Importantly, with no need for 301 the disruption of the tissue architecture or interference with the cellular microenvironment. Additional support in favor of the hepatic origin of plasma labeled transcripts can be found in 359 fragments originating from protein coding genes. These protein coding fragments demonstrate a 360 significant enrichment for liver specific and highly expressed genes, whilst transcripts 361 constitutively depleted in pull-down RNA demonstrate an enrichment for bone marrow specific 362 protein coding fragments, genes related to hematopoietic differentiation and genes specific to 363 neutrophil function. (Figure 5d and sup. table 11) . This result may suggests that the 364 hematopoietic system is one of the major contributors of circulating RNAs. HFD and LFD specific 365 pulled-down protein coding transcripts demonstrate differential enrichment for annotations 366 including adipocytokine signaling and mitochondrial electron transport respectively (Figure 5e ).