Oral Presentation Multi-Omics Conference 2024

Applying STOmics to determine the organisation of cell populations within pluripotent stem cell derived organoids. (#41)

Natalie Charitakis 1 2 3 , Maria Nucera 1 2 3 , Ryan Leung 1 2 , Anna Leichter 1 3 , Lynn Rowley 1 3 , Emma Scully 1 3 , Ritika Saxena 1 2 3 , Alexander Maytum 1 3 , Michelle Scurr 1 3 , Natasha Tuano 1 3 , Holly Voges 1 3 , Hieu Nim 1 3 , Xiaohuan Sun 4 , Bicheng Yang 4 , Ka Leung Li 4 , Marie Faux 1 2 , David Eisenstat 1 2 , Andrew Elefanty 1 2 3 , Shireen Lamande 1 2 3 , Kynan Lawlor 1 2 3 , Jessica Vanslambrouck 1 2 3 , Melissa Little 1 3 , Richard Mills 1 3 , Elizabeth Ng 1 3 , Fernando Rossello 1 3 5 6 , Ed Stanley 1 3 , Rhiannon Werder 1 3 , Silvia Velasco 1 2 3 , David A Elliott 1 2 3 , Enzo R Porrello 1 2 3 7 , Mirana Ramialison 1 2 3
  1. Stem Cell Biology, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  2. Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
  3. Novo Nordisk Foundation Center of Stem Cell Medicine, Parkville, Victoria, Australia
  4. BGI, Brisbane, Queensland, Australia
  5. Medicine, Dentistry and Health Sciences, Univeristy of Melbourne, Melbourne, Victoria, Aus
  6. Medicine, Dentistry and Health Sciences, Univeristy of Melbourne, Melbourne, Victoria, Australia
  7. Department of Anatomy and Physiology, University of Melbourne, Parkville, Victoria, Australia

Spatial transcriptomics (ST) is a novel, disruptive technology that permits exploration of gene regulatory networks with spatial and temporal resolution. The insight provided by ST platforms promises to shed new light on developmental biology across an array of tissue types including organoids. Organoids offer the opportunity to model development and disease while overcoming many of the limitations of animal models or 2D cell cultures. As organoids can be cultured from genetically engineered stem cell and patient cell lines, they permit the detailed analysis of the transcriptional perturbations that underlie disease pathogenesis. 

Organoids display 3D organisation in vitro, making them prime candidates for exploration with ST. However, due to the limitations of commercially available ST technologies and the small size of organoids, there have been relatively few studies using ST to investigate organoids. Furthermore, they have been limited to exploration of a single type of organoid at a time. Here we present the use of STOmics, currently the only ST platform to offer sub-cellular resolution while capturing transcriptome-wide information, to profile an array of organoids including:  brain, heart, kidney, lung, cartilage,  blood and engineered heart valve tissue.  Our data demonstrates the varied utility of the STOmics platform to determine the organisation of cell populations within this range of pluripotent stem cell derived organoids, with certain tissues requiring further optimisation. Furthermore, we provide examples of profiling multiple organoids from a single chip to maximise data capture. 

With current exploration of organoid structure and transcriptional signatures limited in their scope, a more thorough understanding of the localised gene expression driving organisation within each system is needed to generate organoids more closely resembling human organs. By providing a systematic overview of ST data across these varied tissue types, this study illustrates the power of ST to improve our understanding of human organoids.