To make the human liver accessible to metabolic treatments, we employed a liver-specific humanized mouse model in which approximately 50% of the mouse hepatocytes were replaced by human ones. To capture transcriptomes reflecting pathophysiology and therapeutic development of metabolic diseases, we subjected the humanized mice to dietary intervention and the key metabolic transcriptional factor agonist treatments. We then performed rna exoression profiling analysis using data obtained from nanopore direct RNA sequencing of these humanized mice. Overall design: For the dietary treatment, the humanized mice were allowed free access to food (AL, n=4 for donor1, n=3 for donor2) or subjected to a twenty-four hours food withdrawal (Fast, n=4 for donor1, n=3 for donor2). For the transcription factor agonist treatments, the humanized mice were injected with DMSO (n=4), fenofibrate (n=4, 50mg/kg, Sigma-Aldrich, Cat. F6020), rosiglitazone (n=4,10mg/kg, Sigma-Aldrich, Cat. R2408) and GW4064 (n=4, 30mg/kg, Sigma-Aldrich, Cat. G5172) by i.p. injection. The livers were collected after 6 hours fasting and stored in liquid nitrogen immediately after mice sacrificed.The 75 ug of fresh Trizol isolated RNAs were adjusted to a volume of 100 μL with nuclease-free water. The polyadenylated RNAs were selected using the Dynabeads™ mRNA Purification Kit (Invitrogen, Cat. 61006) following the manufacturer's instructions. The 500 ng of fresh isolated polyadenylated RNAs were used for nanopore direct RNA sequencing (DRS) generally following the Oxford Nanopore Technologies (ONT) SQK-RNA002 kit protocol, including the optional reverse transcription step recommended by ONT. Libraries were loaded onto ONT R9.4 flow cells (Oxford Nanopore Technologies) and were sequenced using the GridION platform, with the standard MinKNOW/19.12.5 protocol script being used. UPDATE: [12-13-2024] The following files were updated: GSE224278_all.human.isoforms.donor1.bed.gz GSE224278_all.mouse.isoforms.donor1.bed.gz GSE224278_human.isoforms.donor1.gtf.gz GSE224278_mouse.isoforms.donor1.gtf.gz GSE224278_nanopore_human_transcripts_tpm_donor1.txt.gz