qes-ANRcs’5The human genome is a complex entanglement of DNA strands with exqui-14ClosedPromoterEnhancerOpenOpenClosedChr 10GenotypeExpression profileiPSC+=Genotype-Expression associationCell-Gene Regulatory networkI. Identification of Regulatory Elements 5’ single cell RNA-seqIII. Revealing Interactions of Elements Single molecule Oxford Nanopore TechnologyII. Inferring Genetic AssociationsSingle cell eQTLIV. Functional CharacterizationCRISPR/Multiplex technologyOrganoidssite coordination amongst gene regulatory elements to switch a gene on and off. Understanding how our genome can sense the correct regulatory part-ners to trigger gene activation or repression – especially in a highly compact environment – requires a comprehensive profiling of DNA, RNA and protein features and their interactions with one another. Unraveling this mystery will shed light on novel ways to decipher the regulatory elements in the human ge-nome to correctly identify the causality of genetic disorders, to rectify cellular malfunctions, reengineer cells, and possibly extend the lifespan of vital organs.One of our strategies involves the implementation of single-cell 5’ RNA-seq to profile the coding and non-coding regulatory activities in human cells. As part of the Single Cell Medical Network Program, we profiled thousands of single cells from various human tissues, including the colon, kidney, muscles, lung, and blood and we systematically annotated cis-regulatory elements across hundreds of cell types and states. The lab further explored these gene regula-tory elements by genetic associations including single-cell eQTL, as part of the Human Cell Atlas Asia project, and chromatin-chromatin interactions using the third generation DNA sequencer to elucidate long-range chromatin inter-actions at single cell resolution. We specialize in gene-targeting tools, such as CRISPR-interference and antisense oligonucleotides, to elucidate the functional involvement of cis-regulatory RNAs and elements in human stem cell differen-tiation, brain development, and reprogramming.Figure: Unraveling the gene regulatory ele-ments of the human genomeI) First we identify regulatory elements using single cell 5’ RNA-seq, which reveals promoter and enhancer RNAs. II) We use a multiplex strategy to profile human PMBCs from a large cohort and associate their genotype with gene expression, III) We explore chromatin interactions of regulatory elements by using a third generation DNA sequencer and IV) functionally characterize these interactions with gene perturbation strategies including CRISPR.Recent Major PublicationsDucoli L, Agrawal S, Sibler E, Kouno T, Tacconi C, Hon CC, Berger SD, Müllhaupt D, He Y, Kim J, D’Addio M, Dieterich LC, Carninci P, de Hoon MJL, Shin JW*, Detmar M*. LETR1 is a lymphatic endothelial-specific lncRNA that governs cell proliferation and migration through KLF4 and SEMA3C. Nat Commun 12, 925 (2021)Rozenblatt-Rosen O, Shin JW, Rood JE, Hupalowska A, HCA STWG, Regev A, Heyn. Building a high-quality Hu-man Cell Atlas. Nat Biotechnol 39, 149-153 (2021)Ramilowski JA, Yip CW, Agrawal S, Chang JC, Ciani Y, Kulakovskiy IV, Mendez M, Ooi JLC, Ouyang JF, Parkinson N, Petri A, Roos L, Severin J, Yasuzawa K, Abugessaisa I, Akalin A, Antonov IV, Arner E, Bonetti A, Bono H, Borsari B, Brombacher F, Cameron CJ,… Cannistraci CV, Carde-nas R, Cardon M, Chang H, Dostie J, Ducoli L, Favorov A, Fort A, Forrest ARR, Guigó R, Hoffman MM, Hon CC, Kasukawa T, Kauppinen S, Kere J, Lenhard B, Schneider C, Suzuki H, Yagi K, de Hoon MJL*, Shin JW*, Carninci P*. Functional Annotation of Human Long Non-Coding RNAs via Molecular Phenotyping. Genome Res 30, 1060-1072 (2020)Invited presentationsShin JW. “Building the Human Gene Regulatory Atlas” Cold Spring Harbor Asia (Suzhou, China/Online) October 2020Shin JW. “Human Cell Atlas Asia” The 4th Human Cell Atlas Asia Annual Meeting (Zhejiang, China/Online) October 2020Shin JW. “The Human Cell Atlas” Single Cell Genomics in Biomedical Science Symposium (Melbourne, Australia/Online) September 2020Shin JW. “Building the Human Gene Regulatory Atlas” 10X User Group Meeting in Asia Pacific (Online) May 2020Shin JW. “Building Communities Around Single Cell Ge-nomics” The 1st Human Single Cell Atlas Meeting Seoul National University (Seoul, South Korea) January 2020Laboratory for Advanced Genomics CircuitTeam Leader: Jay W. Shin
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