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Deciphering gene regulatory programs in mouse embryonic skin through single-cell multiomics analysis
Qiuting Deng1,2,3, Pengfei Cai1,2,4, Yingjie Luo1,5
1BGI Research, Shenzhen, 518083, China.
Genome Biology
|July 2, 2025
Summary
We developed high-throughput single-cell chromatin accessibility and transcriptome sequencing (HT-scCAT-seq) to study embryonic mouse skin development. This method reveals gene regulatory mechanisms controlling skin cell differentiation and development.
Area of Science:
- Developmental Biology
- Genomics
- Epigenetics
Background:
- Cell type-specific transcriptional heterogeneity in embryonic mouse skin is known, but regulatory mechanisms remain understudied.
- Existing methods lack the ability to simultaneously profile transcriptome and chromatin accessibility at single-cell resolution.
- Investigating gene regulatory mechanisms is crucial for understanding embryonic skin development.
Purpose of the Study:
- To introduce and validate high-throughput single-cell chromatin accessibility and transcriptome sequencing (HT-scCAT-seq) for dissecting gene regulatory mechanisms.
- To elucidate the regulatory basis of epidermal stratification, periderm terminal differentiation, and fibroblast specification in embryonic mouse skin.
- To identify key regulatory elements and transcription factors involved in embryonic skin development.
Main Methods:
- Development and application of high-throughput single-cell chromatin accessibility and transcriptome sequencing (HT-scCAT-seq).
- Simultaneous profiling of transcriptome and chromatin accessibility in single embryonic mouse skin cells.
- In silico perturbation analysis and CUT&Tag experiments to validate transcription factor roles.
Main Results:
- Identification of candidate cis-regulatory elements (cCREs) and their target genes critical for dermal and epidermal development.
- Observation of distinct chromatin accessibility states in cells with similar gene expression profiles during periderm differentiation.
- Characterization of ALX4 and RUNX2 as potential transcription factor regulators of dermal papilla lineage development.
Conclusions:
- HT-scCAT-seq is a powerful tool for studying spatiotemporal gene regulation dynamics in single cells.
- The findings enhance the understanding of embryonic skin development.
- The study provides a scalable framework for investigating regulatory mechanisms in various biological systems and diseases.
