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Updated: Sep 9, 2025
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Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
Published on: July 6, 2022
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Spatial joint profiling of DNA methylome and transcriptome in tissues
Chin Nien Lee1,2, Hongxiang Fu3,4,5, Angelysia Cardilla3,5
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. chinnien.lee@pennmedicine.upenn.edu.
Nature
|September 3, 2025
Summary
Researchers developed a new method for whole-genome spatial co-profiling of DNA methylation and transcriptome. This technique maps epigenetic marks and gene expression in the same tissue section, advancing spatial omics for developmental and brain studies.
Area of Science:
- Epigenetics and Genomics
- Developmental Biology
- Neuroscience
Background:
- Spatial resolution is crucial for understanding tissue biology and cellular functions.
- Existing spatial omics methods lack the capacity to profile DNA methylation alongside other omics data.
- DNA methylation is a key epigenetic mark regulating gene expression.
Purpose of the Study:
- To introduce a novel method for whole-genome spatial co-profiling of DNA methylation and transcriptome.
- To enable near single-cell resolution mapping of both DNA methylation and RNA expression in the same tissue section.
- To explore the interplay between DNA methylation and gene expression in mammalian development and brain function.
Main Methods:
- Development of a new technology for simultaneous spatial profiling of DNA methylation and transcriptome.
- Application of the method to mouse embryos during development and the postnatal mouse brain.
- Generation of DNA-RNA bimodal tissue maps at near single-cell resolution.
Main Results:
- Creation of detailed spatial maps revealing the interplay between DNA methylation and gene expression.
- Identification of synergistic molecular definitions of cell identity through spatial patterns of methylation and transcriptome.
- Reconstruction of developmental dynamics in mouse embryogenesis, highlighting methylation-mediated transcriptional regulation.
Conclusions:
- The developed method successfully extends spatial omics to include DNA cytosine methylation.
- This technology provides a comprehensive understanding of tissue biology, development, and disease.
- The findings offer new insights into spatial programming, cell identity, and epigenetic regulation in mammals.
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