lncRNAs in dendritic cell differentiation

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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) play a pivotal role as antigen-presenting cells, serving as the orchestrators 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 human long noncoding RNAs (lncRNAs) 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 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 timecourse, many of which could be potentially influencing expression of various mRNAs required to establish mature functional DC1s.

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

Project Specific Aims

  • create comprehenisve atlas of lncRNA in DC1 differentiation
  • genomic & epigenomic classification of lncRNAs, including 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 (subcelluar localization, sequence motifs, binding motifs, etc.)

Methods & Data

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

JSPS Postdoc Needed

We are looking for JSPS Postdoc applicants with skills in:
1. Bioinformatics/AI (willing to learn relevant biology), and/or
2. Biology (willing to learn bioinformatics)

Questions or interested joining us for a JSPS postdoc ? Please email Jordan 📧 .

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