Most of the human genome is considered non-coding, yet we and others 16Atlas of Transcribed cis regulatory Elementshave found a plethora of regulatory elements – in the form of either RNA or DNA – to regulate gene expression. How they control gene expres-sion across a multitude of cell types and disease states is not well understood. In my lab, we holistically interrogate gene regulation mediated by non-coding regulatory elements through the implementation of single-cell 5’ RNA-seq. We actively collaborate with medical institutions in Japan to map single cells using spatial and single cell transcriptomics across human tissues. In collaboration with Dr. Chung Chau Hon’s laboratory (IMS), we developed a computational algorithm to annotate cis-regulatory elements, including enhancer RNAs, at single cell resolution. We are using these tools to interrogate cis-regulatory ele-ments in association with genetic disorders based on single-cell eQTL, as part of the Human Cell Atlas (HCA) Asia project (funded by the Chan Zuckerberg Initiative), and chromatin-chromatin interactions at single cell resolution using long-read DNA sequencers (funded by the Japan Agency for Medical Research and Development, AMED).The lab also specializes in gene-targeting tools, including CRISPR-inter-ference and antisense oligonucleotides, to elucidate the functional role of long non-coding RNAs in human stem cells, brain development, and cell reprogram-ming. We are combining gene perturbation methods with single-cell genomics to elucidate non-coding regulatory elements in human brain organoid models in a scalable and cost-effective manner. As part of the FANTOM6, we are ana-lyzing non-coding regulatory elements by their associated molecular pathways and interacting partners, including DNA-DNA, DNA-RNA and RNA-protein interactions, to intervene and modulate gene regulation for potential therapeu-tic modalities.Figure: A) The Atlas of Transcribed cis Regulatory Elements across human tissues reveals hierarchical and complex heterogeneity of cell types and states at the single cell resolution using the 5’ RNA profiling methodology. B) A systematic perturbation of long non-coding RNAs reveal cis-regulatory features of lncRNA in a cell-type depen-dent manner.Recent Major PublicationsYip CW, Hon CC, Yasuzawa K, Sivaraman DM, Ramilowski JA, Shibayama Y, Agrawal S, Prabhu AV, Parr C, Severin J, Lan YJ, Dostie J, Petri A, Nishiyori-Sueki H, Tagami M, Itoh M, López-Redondo F, Kouno T, Chang JC, Luginbühl J, Kato M, Murata M, Yip WH, Shu X, Abugessaisa I, Hasegawa A, Suzuki H, Kauppinen S, Yagi K, Okazaki Y, Kasukawa T, de Hoon M, Carninci P, Shin JW*. Antisense-oligonucleotide-mediated perturbation of long non-coding RNA reveals functional features in stem cells and across cell types. Cell Reports 41, 111893 (2022)Moody J, Kouno T, Chang JC, Ando Y, Carninci P, Shin JW*, Hon CC. SCAFE: a software suite for analysis of transcribed cis-regulatory elements in single cells. Bio-informatics 38, 5126-5128 (2022)Jinzhuang Dou, Yukun Tan, Kian Hong Kock, Jun Wang, Xuesen Cheng, Le Min Tan, Kyung Yeon Han, Chung-Chau Hon, Woong-Yang Park, Shin JW, Haijing Jin, Yujia Wang, Han Chen, Li Ding, Shyam Prabhakar, Nicholas Navin, Rui Chen, Ken Chen. Single-nucleotide variant calling in single-cell sequencing data with Monopogen. Nature biotechnology 1-10 (2023)Invited presentationsShin J., Keynote speaker/panelist. “Scaling up single cell genomics for science and medicine” HCA Asia Meeting (Kolkata, India) November 2023Shin J., “Single cell atlas of transcribed cis-regulatory elements in the human genome”, Seoul National Uni-versity – Genome Medicine Institute (virtual) November 2023Shin J., “Single cell atlas of transcribed cis-regulatory elements in the human genome”, Korean Society of Bioinformatic (KSBi) (Yeosu, South Korea) November 2023Shin J., “Single cell atlas of transcribed cis-regulatory elements in the human genome”, Karolinska Institute/SciLife Lab (Stockholm, Sweden) September 2023Shin J. “Atlas of transcribed CRE reveals disease associ-ated regulatory modules in instinct cell populations” HCA General Meeting (Toronto, Canada) July 2023ABLaboratory for Advanced Genomics CircuitTeam Leader: Jay W. Shin
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