A Collaborative Effort to Map the Spatial Biology of Organoids

For the last decade or so, scientists have been able to use stem cells to grow three-dimensional models of human tissue in the lab, called organoids, to better understand disease and advance new treatments and therapies.

Understanding how cells are organised within stem cell–derived organoids is critical if these models are to reliably mimic human tissues.

In a new study published in iScience, researchers from the reNEW Melbourne node showcase a highly collaborative approach to tackling this challenge using advanced spatial transcriptomics technology.

The study brings together expertise from across the reNEW Melbourne, based at Murdoch Children’s Research Institute (MCRI) and labs in the MCRI Stem Cell Medicine theme to profile eight different human organoids in parallel, including models of brain, heart, kidney, lung, cartilage and blood-forming tissues.

Using the Stereo-seq spatial transcriptomics platform, the team developed and optimised new workflows that allow multiple organoids of the same tissue type to be analysed on a single chip – improving efficiency, reducing cost, and minimising technical variation.

Beyond experimental advances, the team also developed a new computational approach that enables spatial analysis of organoids even when traditional single-cell resolution is difficult to achieve.

“At the heart of this work is collaboration. The project was driven by multidisciplinary PhD students Maria Nucera and Ryan Leung as well as Senior Research Officer Dr Natalie Charitakis, supported and mentored across multiple reNEW Melbourne and SCM laboratories,” said Professor Mirana Ramialison, senior author of the paper.

Professor Ramialison and A/Professor Fernando Rossello co-lead of the reNEW Bioinformatics hub, a platform for reNEW researchers that provides support from experimental design to analysis and publication. 

“One thing our study is open about is the current limitations in the field. Achieving consistent single-cell resolution in small, complex organoids remains challenging,” said first author Maira Nucera, a PhD student in the Neural Stem Cells group, led by PI A/Prof Silvia Velasco, and co-supervised by the Transcriptomics and Bioinformatics group.

However, the authors emphasise that spatial transcriptomics is evolving rapidly, and that continued improvements in chemistry, imaging and analysis are likely to soon make these approaches a standard screening tool for organoid research.

“Our findings demonstrates that despite the challenges in reaching single-cell resolution, spatial transcriptomics is a rapidly advancing field and shows promise for wider adoption as a standard screening methods for organoids,” said A/Prof Rossello, lead contact for the study.