The human genome is a complex entanglement of DNA strands with ex-16quisite coordination amongst gene regulatory elements to switch a gene on and off. Understanding how our genome can sense the correct regulatory partners to trigger gene activation or repression – especially in a highly com-pact environment – requires a comprehensive profiling of DNA, RNA and pro-tein features and their interactions with one another. Unraveling this mystery will shed light on novel ways to decipher the regulatory elements in the human genome, enabling us to correctly identify the causality of genetic disorders, to rectify cellular malfunctions, to reengineer cells, and possibly to 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: Single Cell Clustering Across 15 Human Tissues Based on 5’ RNA-seqSingle cells are clustered based on similarities in cis-regulatory elements (UMAP projection). For each tissue, distinct cell types are highlighted, revealing a vast diversity of human cells.Recent Major PublicationsLuginbühl J, Kouno T, Nakano R, Chater TE, Sivaraman DM, Kishima M, Roudnicky F, Carninci P, Plessy C, Shin JW. Decoding neuronal diversification by multiplexed single-cell RNA-seq. Stem Cell Rep 16, 810-824 (2021)Ducoli 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; Human Cell Atlas Standards and Technology Working Group, Regev A, Heyn H. Building a high-quality Human Cell Atlas. Nat Biotechnol 39, 149-153 (2021)Invited presentationsShin JW. “Decoding Neuronal Diversification by Multi-plexed Single Cell RNA-seq” Keio University - Stanford University Joint Seminar (Tokyo, Japan/Online) October 2021Shin JW. “Human Cell Atlasing the Transcribed Cis-Regulatory Elements” CZI Single-Cell Biology Annual Meeting (Paolo Alto, USA/Online) October 2021Shin JW. “Functional Elucidation of Gene Regulatory Ele-ments in Brain Development” The 64th Japanese Society of Neurochemistry Annual Meeting (Nara, Japan/Online) September 2021Shin JW. “Building the Human Cell Regulatory Atlas” The 19th Protein Island Matsuyama International Sympo-sium (Ehime, Japan/Online) September 2021Shin JW. “Decoding Neuronal Diversification by Multi-plexed Single Cell RNA-seq” International Society for Stem Cell Research - Computational Workshop (Online) March 2021Laboratory for Advanced Genomic CircuitTeam Leader: Jay W. Shin
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