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<p>The three-dimensional (3D) organization of <i>cis</i>-regulatory elements (CREs) is critical in transcription control. However, capturing transcriptome, epigenome and 3D genome from the same single cells remains challenging. Here we present scHiCAR (single-cell Hi-C with assay for transposase-accessible chromatin and RNA sequencing), a plate-based combinatorial barcoding method that simultaneously profiles mRNA, open chromatin and chromosome conformation capture from the same cells. Compared to existing single-cell 3D genome methods, scHiCAR more efficiently enriches long-range <i>cis</i>-interactions anchored at candidate CREs (cCREs). Applied to 1.62 million mouse brain cells and complemented with a deep-learning-based loop caller, scHiCAR accurately defines cell-type-specific transcriptomes, accessible cCREs and 5-kb-resolution enhancer–promoter pairs across 22 brain cell types. scHiCAR also performs robustly in challenging tissues such as skeletal muscle, enabling trimodal single-cell-level analysis of gene regulation dynamics during muscle stem cell regeneration. By providing a scalable and cost-effective system for single-cell trimodal analysis of gene-regulatory landscapes in complex tissues, scHiCAR reveals gene-locus-specific regulatory roles of 3D genome reorganization in transcriptional control.</p>

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Trimodal single-cell profiling of transcriptome, epigenome and 3D genome in complex tissues with scHiCAR

  • 期刊论文

  • 发表日期：

    2026年2月19日

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  • Xiaolin Wei,
  • Yueyuan Xu,
  • Dongchan Yang,
  • Kyukwang Kim,
  • Lizhi Yi,
  • Wenzhe Luo,
  • Xin Lin,
  • Yu Xiang,
  • Ashley B. Williams,
  • Xiaotao Wang,
  • Sweta Srivas,
  • Christabel Tan,
  • Kan Zhang,
  • Wei Li,
  • Yang Eric Li,
  • Feng Yue,
  • Z. Josh Huang,
  • Inkyung Jung,
  • Yarui Diao

摘要

The three-dimensional (3D) organization of cis-regulatory elements (CREs) is critical in transcription control. However, capturing transcriptome, epigenome and 3D genome from the same single cells remains challenging. Here we present scHiCAR (single-cell Hi-C with assay for transposase-accessible chromatin and RNA sequencing), a plate-based combinatorial barcoding method that simultaneously profiles mRNA, open chromatin and chromosome conformation capture from the same cells. Compared to existing single-cell 3D genome methods, scHiCAR more efficiently enriches long-range cis-interactions anchored at candidate CREs (cCREs). Applied to 1.62 million mouse brain cells and complemented with a deep-learning-based loop caller, scHiCAR accurately defines cell-type-specific transcriptomes, accessible cCREs and 5-kb-resolution enhancer–promoter pairs across 22 brain cell types. scHiCAR also performs robustly in challenging tissues such as skeletal muscle, enabling trimodal single-cell-level analysis of gene regulation dynamics during muscle stem cell regeneration. By providing a scalable and cost-effective system for single-cell trimodal analysis of gene-regulatory landscapes in complex tissues, scHiCAR reveals gene-locus-specific regulatory roles of 3D genome reorganization in transcriptional control.