69eases is one of the fundamental goals of the Human Cell Regulatory Atlas project in IMS. Using 5’end single-cell RNA-seq technology, which captures the transcription start sites, the proj-ect aims to measure the activities of transcribed cis-regulatory elements (tCRE), including promoters and enhancers, in various cell-types and -states across multiple human organs. This project is made possible through an extensive collaborative network in-volving RIKEN and medical institutions across Japan for sample collection. We generated a tCRE atlas of 436,910 cells from 23 elucidate the function of the mammalian genome. The 6th phase of the FANTOM project aims at creating a comprehensive catalog of functional lncRNAs. We created a lncRNA knockdown data set on cell growth and morphology using real-time imag-ing and CAGE deep sequencing to reveal molecular pathways associated with each lncRNA in human primary fibroblast cells (Ramilowski et al. Genome Research 2020).FANTOM6 also found that the majority of lncRNAs reside in the nucleus and 35% of lncRNAs are chromatin-bound. In order to analyze RNA-chromatin interactions, we developed a new technology named RNA And DNA Interacting Complexes Li-gated and sequenced (RADICL-seq) that precisely maps genome-wide RNA-chromatin interactions in intact nuclei (Bonetti et al. Nature Communications 2020). Interactome analysis by RADICL-seq revealed distinct genome occupancy patterns for specific tissues, defining over 100 distinct cell-subtypes (Figure). This tCRE atlas will enable us to interrogate the cell-type specific cir-cuits of gene regulation and assess their contribution to disease predisposition through integration with genetic data. One of our goals is to identify critical cell types and cellular processes for various diseases. The Human Cell Regulatory Atlas in IMS will facilitate discovery of new biology and, at the same time, build a comprehensive integrative database to power the next generation artificial intelligence to solve health and medical needs that we are facing in our lifetime.classes of transcripts in each cell type. Interestingly, we found that most interactions in cis were from the intronic regions of protein-coding transcripts whereas interactions in trans were from the exonic regions of non-coding transcripts, which indicates the possibility that the intronic regions of protein-coding transcripts play a regulatory role in gene expression.After the study on fibroblast cells, the project will proceed with knockdown analysis of lncRNAs in iPS cells to understand the lncRNA properties in stem cells.Figure: A tCRE atlas from 23 human tissues. A) A single-cell UMAP consists of 436,910 cells, divided into 11 major cell-types. B) Sub-clustering of the 11 major cell-types, defining over 100 distinct cell-subtypes.Figure: Cell-type-specific RNA-chromatin interaction patterns. Circos plots depicting genomic interactions of the Neat1 lncRNA in mouse embryonic stem cells (mESCs) and mouse oligodendrocyte progenitor cells (mOPCs).The Human Cell Regulatory AtlasDetermining the relevance of cell-types and -states to dis-FANTOMThe FANTOM consortium was established in the year 2000 to
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