RNA - Genetherapys

Introducing a New Method for 3D Tissue Spatial Mapping

In biomedical research, spatial transcriptomics is a molecular profiling tool that maps DNA, RNA, and proteins in tissue, which is especially interesting for those involved in developmental biology, cancer, immunology, and neuroscience. Funded by the National Center for Gene Therapy and Drugs based on RNA Technology, Spoke 2 researchers from the Sapienza University of Rome offer a new open-source spatial transcriptomics platform, called Open-ST, which generates 3D maps of diseased tissue cells.

Published in Cell, the collaborative work behind Open-ST: High-resolution spatial transcriptomics in 3D which includes the Max Delbrück Center in Berlin and the University of Milan will enable researchers to reconstruct and map out gene expression three-dimensionally.

Streamlining protocols towards precision medicine, the high resolution of the Open-ST platform can distinguish molecular and subcellular structures that are unseen in traditional 2D representations. Accessing a three-dimensional visual output of diseased tissue is a goal of many clinical research projects in the field of pathology and physiology, but making this technology cost-effective and accessible has long been missing.

Until recently, performing detailed molecular analyses was not possible as available techniques could only obtain average values referred to a large number of molecules. Not only does Open-ST allow researchers to study the aspects of each cell and therefore their specific molecular contribution within a sample using “single-cell omics”, but it also allows researchers to define the spatial localization of each cell within a tissue.

Previously available ST technology could characterize molecules transcribed from each gene while preserving their localization but was limited due to high costs and poor resolution regarding the sensitivity in defining molecules in each single cell. As a result, the protocols behind Open-ST contain a precise sequence of experimental steps, including the analysis of molecular markers, the division of the cell into subunits, and finally the editing and digital visualization of the data through specially developed software.

Demonstrating its validity and efficiency, the international team tested cells taken from various types of tissues. Results from healthy and metastatic lymph nodes from patients with head and neck cancer correctly analyzed the high variability of the samples’ genetic code. The Open-ST approach can help scientists identify biomarkers, which is useful for the characterization of the tumor tissue itself.

Microscopic image of breast cancer cells resisting treatment

Prof Elisabetta Ferretti of the Department of Experimental Medicine shares how Open-ST came to fruition, “The work was a collaboration between Prof Giuseppe Macino, Professor Emeritus of Sapienza and President of the Forge Foundation of Udine, Prof Nikolaus Rajewsky, Director of the Laboratory of Systems Biology of Gene Regulatory Elements of the Berlin Institute for Medical Systems Biology of the Max Delbrück Center, and Prof Massimiliano Pagani of the University of Milan and IFOM Director of the Laboratory of Molecular Oncology and Immunology.”

Postdoctoral Researcher and first author of the study, Dr Elena Splendiani of Sapienza University in Rome comments, “RNA transcripts are fundamental molecules that transmit information contained in each gene. Measuring their quantity with the new Open-ST technology allows researchers to not only define them accurately but also distinguish their distribution on an intracellular level. This 3D viewpoint of each single cell allows us to obtain new information on the positioning and communication between the cells themselves. Compared against other spatial technologies, the novel and wide applicability of Open-ST offers the first method to analyze both healthy and tumor tissue.”

Prof Macino offers insight, “The 3D high-resolution images produced with Open-ST identified ten tumor cell subtypes present in primary and metastatic tumors, defining details of tumor heterogeneity never seen before.”

Prof Ferretti and Prof Macino look towards the future, “In the growing field of precision medicine, our results offer solutions towards better understanding RNA molecules in the development of gene therapy by defining biomarkers for the diagnosis and management of disease.”

The scientific development behind Open-ST was made possible thanks to the European Union National Recovery and Resilience Plan, Next Generation EU, and funding from the Italian Ministry of University and Research facilitated by the National Center for Gene Therapy and Drugs with RNA Technology.

Written by

The Foundation’s editorial staff

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