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Background <p>Cell type-specific transcriptional heterogeneity in embryonic mouse skin is well-documented, but few studies have investigated the regulatory mechanisms. Here, we present high-throughput single-cell chromatin accessibility and transcriptome sequencing (HT-scCAT-seq), a method that simultaneously profiles transcriptome and chromatin accessibility. We utilized HT-scCAT-seq to dissect the gene regulatory mechanism governing epidermal stratification, periderm terminal differentiation, and fibroblast specification.</p> Results <p>By linking chromatin accessibility to gene expression, we identify candidate <i>cis-</i>regulatory elements (cCREs) and their target genes which are crucial for dermal and epidermal development. We describe cells with similar gene expression profiles that exhibit distinct chromatin accessibility statuses during periderm terminal differentiation. Finally, we characterize the underlying lineage-determining transcription factors and demonstrate that ALX4 and RUNX2 are candidate transcription factors regulators of the dermal papilla lineage development through in silico perturbation analysis and CUT&amp;Tag experiment.</p> Conclusions <p>Overall, HT-scCAT-seq represents a powerful tool for unraveling the spatiotemporal dynamics of gene regulation in single cells. Our results advance the understanding of embryonic skin development while providing a scalable framework for investigating regulatory mechanisms across diverse biological systems and disease contexts.</p>

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Deciphering gene regulatory programs in mouse embryonic skin through single-cell multiomics analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

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  • Qiuting Deng,
  • Pengfei Cai,
  • Yingjie Luo,
  • Zhongjin Zhang,
  • Wen Ma,
  • Zijie Huang,
  • Xiaoya Chen,
  • Shijie Hao,
  • Weiguang Ma,
  • Jiangshan Xu,
  • Chunqing Wang,
  • Mengnan Cheng,
  • Xiumei Lin,
  • Ru Zhou,
  • Shanshan Duan,
  • Junjie Chen,
  • Ronghai Li,
  • Xuyang Shi,
  • Chang Liu,
  • Liang Wu,
  • Peng Gao,
  • Jianting Li,
  • Xiao Yang,
  • Xiangdong Wang,
  • Jun Xie,
  • Longqi Liu,
  • Yue Yuan,
  • Chuanyu Liu

摘要

Background

Cell type-specific transcriptional heterogeneity in embryonic mouse skin is well-documented, but few studies have investigated the regulatory mechanisms. Here, we present high-throughput single-cell chromatin accessibility and transcriptome sequencing (HT-scCAT-seq), a method that simultaneously profiles transcriptome and chromatin accessibility. We utilized HT-scCAT-seq to dissect the gene regulatory mechanism governing epidermal stratification, periderm terminal differentiation, and fibroblast specification.

Results

By linking chromatin accessibility to gene expression, we identify candidate cis-regulatory elements (cCREs) and their target genes which are crucial for dermal and epidermal development. We describe cells with similar gene expression profiles that exhibit distinct chromatin accessibility statuses during periderm terminal differentiation. Finally, we characterize the underlying lineage-determining transcription factors and demonstrate that ALX4 and RUNX2 are candidate transcription factors regulators of the dermal papilla lineage development through in silico perturbation analysis and CUT&Tag experiment.

Conclusions

Overall, HT-scCAT-seq represents a powerful tool for unraveling the spatiotemporal dynamics of gene regulation in single cells. Our results advance the understanding of embryonic skin development while providing a scalable framework for investigating regulatory mechanisms across diverse biological systems and disease contexts.