Page 54 - GPD-4-3

Gene & Protein in Disease

REVIEW ARTICLE
In situ spatial profiling: Gaining molecular

and cellular insights within content and context

†
†
Shu-Ti Lin , Ian Molyneaux, and Chen Yeh *
Department of Oncology, OncoDxRx, Los Angeles, California, United States of America

Abstract

For years, valuable clinical samples preserved in formalin-fixed paraffin-embedded
tissues were underutilized. However, with advanced spatial multiomics profiling
tools, crucial information has become increasingly accessible. Integrating genomic
data with spatial information has unveiled crucial insights into cellular activities,
enhancing our comprehension of biology. Measuring cellular gene expression while
capturing spatial context – including morphology and intercellular relationships –
is vital for understanding both normal and diseased biological processes. To date,
this approach has illuminated the mechanisms of complex diseases, such as cancer
and has facilitated the discovery of biomarkers for early disease detection and new
† These authors contributed equally therapeutic targets, accelerating progress in cancer immunotherapies. Cutting-edge
to this work. single-cell analysis tools are rapidly emerging as the gold standard for investigating
*Corresponding author: intricate biological systems and medical specimens, fueling a multi-billion-dollar
Chen Yeh industry. Single-cell spatial research, in particular, is inherently cross-disciplinary
(cyeh.oncodxrx@gmail.com) and addresses questions that remain hidden when focusing solely on the genome
Citation: Lin S, Molyneaux I, Yeh C. or transcriptome of large cell populations. Leveraging advances in single-cell spatial
In situ spatial profiling: Gaining profiling can offer insights into improving cancer immunotherapy and other modern
molecular and cellular insights medical treatments. This review will delve into the diverse applications of spatial
within content and context.
Gene Protein Dis. profiling technology, showcasing examples that demonstrate its ability to provide
2025;4(3):025050007. a detailed picture of the underlying molecular and cellular mechanisms within
doi: 10.36922/GPD025050007 cells. As a comprehensive reference, this review empowers researchers and industry
Received: January 27, 2025 leaders to harness single-cell and spatial omics for breakthroughs in biomedicine
1st revised: June 4, 2025 and translational science.
2nd revised: June 7, 2025
Keywords: Formalin-fixed paraffin-embedded tissues; Genomics; Single-cell analysis;
Accepted: June 25, 2025
Spatial profiling; Transcriptomics
Published online: July 10, 2025
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the 1. Introduction
Creative Commons Attribution
License, permitting distribution, In situ spatial profiling is a technique used to examine DNA or RNA within specific
and reproduction in any medium,
provided the original work is regions of interest in formalin-fixed paraffin-embedded (FFPE) or fresh, frozen tissue
properly cited. samples. The regions of interest for detailed study can be selected based on their
Publisher’s Note: AccScience location or distinct morphological features within the tissue. These regions can have
Publishing remains neutral with any geometric shape – whether contoured, gridded, segmented, or specific to cell types.
regard to jurisdictional claims in
published maps and institutional Typically, selected regions are up to 600 μm in diameter, and the high resolution of this
affiliations. technique makes single-cell analysis feasible.

Volume 4 Issue 3 (2025) 1 doi: 10.36922/GPD025050007