RIKEN IMS AnnualReport 2020

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GSLBKHNNNNNNENIINNNNENNNNNNNENNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN01Brain01Gut01Lung01Skin01Liver01Bone01Kidney0101010101010101Development010101Rod0101010101Heart010101Cone0101010101Reprod.G cell01010101BrainEyeGutLungGeoMXCODEXDSPtCy-CIFMIBIMultiplexIFSkinLiverKidneySTDNAmicrosc.GeoMXDSPMERFISHscRNASeqATACSeqSlideSeqHDSTSTARMAPSeqFISHsnRNASeqDroNcSeq0101010101010101010101010101010101010101010101010101010101010101010101010101DevelopmentMuscleHeartTISSUECELLSMETHODS65BrLuDevRepCell TypesSingle Cell 5’ RNA-seq to reconstruct the Gene Regulatory NetworkUnraveling the cis-regulatory elements and their associations 
in both health and diseaseGene 
regulationlncRNA (Nucleic acids)Regulatory Motifs
(Regenerative medicine)Epigenetic (Small molecules)Cis-regulatory elements (CRISPR)Genetic variation in non-coding RE (Precision medicine)is one of the fundamental missions of the Human Gene Reg-ulatory Atlas project in IMS. Based on single-cell genomic tech-nologies, the Human Gene Regulatory Atlas aims to define gene-to-cell networks across multiple human organs and delineate their regulatory processes that encompass healthy and disease states. The 5’-focused single-cell RNA-seq technology will reveal gene regulatory elements, including promoter and enhancer ac-year 2000 aiming at exploring the regulatory functions of the mammalian genome. The 6th phase of the FANTOM project pub-lished the world’s largest knockdown dataset of long noncoding RNAs (lncRNAs) as its pilot data (Ramilowski et al. Genome Re-search 2020). Previous FANTOM projects and other study groups revealed that lncRNAs constitute the majority of transcripts in the human genome, but little is known about their functions, although several of them have been found to play important roles in human health. The FANTOM5 project identified 19,175 potentially functional lncRNAs in the human genome (Hon et al. Nature 2017). In order to gain a better understanding about lncRNA functions, FANTOM6 established an automated high-throughput platform for cell culture to systematically knockdown 285 lncRNAs in human primary fibroblasts using the antisense LNA-modified GapmeR antisense oligonucleotide (ASO) tech-nology. The effects of the suppression of lncRNA expression were tivities, and decode cis-regulatory programs to evaluate the risks for genetic disorders. The Human Gene Regulatory Atlas is made possible through an extensive collaborative network involving RIKEN and medical institutions across Japan. The Human Gene Regulatory Atlas in IMS facilitates discovery of new biology and, at the same time, builds a comprehensive integrative database to power the next generation artificial intelligence to solve health and medical needs that we are facing in our lifetime.examined by real-time imaging of cell growth and morphology. The transcriptomic responses in the knockdown analyzed by Capped Analysis of Gene Expression (CAGE) provided deeper insights, with molecular phenotypes associated with the lncRNA functions. Collectively, over 30% of the tested lncRNAs showed the effects of the knockdown on cell growth and morphology. All data are publicly available at https://fantom.gsc.riken.jp/zenbu/reports/#FANTOM6.Figure: The Human Gene Regulatory AtlasBeyond the ‘periodic table’ of the human cell types, the Human Gene Regulatory Atlas aims to elucidate the regulatory processes of individual cells in both health and diseased states. The project relies on single cell 5’ RNA seq and other genomics technologies to decode the regulato-ry elements of the human genome, including non-coding regions. The rich dataset will serve as the foundation to build gene- and cell-regulatory atlases required for next generation precision medicine, drug development and cell-based therapeutics.Figure: Enriched biological pathways across 340 ASOsScale indicates Gene Set Enrichment Analysis (GSEA) enrichment value calculated as -log10 (p) x sign (NES).The Human Gene Regulatory AtlasThe Human Gene Regulatory AtlasPrecise determination of our health status and risk for disease FANTOMFANTOM is an international consortium established in the