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Updated: Jun 11, 2025
Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
Published on: July 6, 2022
Multiplexed spatial mapping of chromatin features, transcriptome, and proteins in tissues
Pengfei Guo1,2, Liran Mao1,3,4,2, Yufan Chen5
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Spatial-Mux-seq enables simultaneous multi-omics profiling, revealing complex cellular identities and regulatory networks in tissues. This advanced spatial multi-omics approach enhances understanding of tissue heterogeneity beyond single-modality studies.
Area of Science:
- Molecular Biology
- Genomics
- Systems Biology
Background:
- Cellular states are regulated by a hierarchy of molecular layers (genome, epigenome, transcriptome, proteome, metabolome).
- Spatial omics technologies capture molecular data within tissue context but are limited to 1-2 modalities, hindering comprehensive cellular identity understanding.
- Existing methods provide incomplete views of complex biological systems and regulatory mechanisms.
Purpose of the Study:
- To introduce spatial-Mux-seq, a novel multi-modal spatial technology.
- To enable simultaneous profiling of five molecular modalities (two histone modifications, open chromatin, transcriptome, proteins) at tissue scale and cellular resolution.
- To advance the understanding of cellular identity and regulatory mechanisms in complex biological systems.
Main Methods:
- Development and application of spatial-Mux-seq technology.
- Simultaneous spatial profiling of genome-wide histone modifications, open chromatin, whole transcriptome, and protein panels.
- Generation of multi-modal tissue maps in mouse embryos and brains.
Main Results:
- Spatial-Mux-seq successfully mapped five molecular modalities in a spatially resolved manner.
- Multi-modal data significantly improved cell type and state discrimination compared to unimodal data.
- Analysis revealed spatiotemporal relationships between epigenetic modifications, gene expression, and protein levels during neuron differentiation.
- Identified a radial glia spatial niche with spatially varying epigenetic gradients and uncovered novel roles for repressive histone marks in the hippocampus.
Conclusions:
- Spatial-Mux-seq provides a comprehensive approach to characterizing tissue and cellular heterogeneity.
- This technology offers unprecedented insights into the interplay between tissue organization, function, and gene regulatory networks.
- The findings open new avenues for investigating complex biological systems and disease mechanisms.
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