Project Support: KAKENHI Grant-in-Aid for Scientific Research (B)
Related Project: lncRNAs in immune cell infection & activation

This study aims to establish the foundation for unraveling the regulatory modes and features of long noncoding RNAs (lncRNAs) in immune and other cell differentiation and to facilitate lncRNA comprehensive functional classification.

Introduction

Dendritic cells (DCs) are pivotal to antigen-presenting and to orchestrating of immune responses. Prior research has demonstrated that the activation of enhancers associated with DC-related genes, facilitated by transcription factors like IRF8, governs lineage specification Kurotaki et al, PNAS, 119 (34) e2207009119, 2022. However, the regulatory mechanisms governing the enhancer landscape and subsequent differentiation remain elusive.

Concurrently, our team created a comprehensive atlas comprising approximately 20,000 long noncoding RNAs (lncRNAs) in humans Hon CC, Ramilowski JA, et al, Nature, 543, 199–204, 2017, and subsequently studied functionalities of nearly 600 lncRNAs in dermal fibroblasts and iPS cells Ramilowski JA, Yip W, et al, Genome Research, 30, 1060-1072, 2020. Nonetheless, the functions of most lncRNAs remain highly diverse and largely unexplored.

Recently we started investigating the roles of lncRNAs in regulating DC type1 (DC1) differentiation. Our preliminary analyses uncovered nearly ~7,000 known and novel lncRNAs expressed in the myeloid differentiation time course, many of which could be potentially influencing the expression of various mRNAs required to establish mature functional DC1s.

Fig: Expression profiles of lncRNAs are much more cell-type restricted than those of mRNAs

Project Specific Aims

• create comprehensive atlas of lncRNA in DC1 differentiation
• genomic & epigenomic classification of lncRNAs, including the discovery of enhancer-derived lncRNAs (e-lncRNAs)
• investigate spatiotemporal relation of lncRNA expression with chromatin landscape events (A/B compartment establishment, chromatin activation, etc) required for making DC1-specific mRNAs
• uncover lncRNA functional features (sub-cellular localization, sequence motifs, binding motifs, etc.)

Methods & Data

We are employing bioinformatics methodologies and proprietary AI algorithms and applying them to multi-omics in-vivo DC1 differentiation data (RNA-seq, ChIP-seq, ATAC-seq, Hi-C, and single cell data).

JSPS Postdoc Needed

PhD Researchers with background in (i) Bioinformatics/AI and/or (ii) Biology (basic bioinformatics skills required) are welcome to apply for JSPS Postdoc with us!

Questions? Interested in joining us? Please email Jordan 📧

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