Kidney Week

Abstract: TH-OR42

Spatial Transcriptomics (ST): Integrating Molecular Profiles with Histomorphology in Kidney Tissue Sections

Session Information

• Pathology of Kidney Diseases: Novel Mechanisms and Clinical Correlations
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Pathology and Lab Medicine

• 1601 Pathology and Lab Medicine: Basic

Authors

• Raghubar, Arti M., The University of Queensland, Saint Lucia, Queensland, Australia

Arti M. Raghubar



Arti Raghubar is a clinical scientist with a special interest in renal cancer and molecular histology. After graduating from Queensland University of Technology with a BAppSci (MedSci) she completed training in a private histology laboratory in Brisbane. She has also completed a MMolBiol (The University of Queensland) by establishing a novel micro-proteomics method to profile Immunoglobulin A Nephropathy. She currently works as a clinical scientist at Anatomical Pathology, Pathology Queensland at The Royal Brisbane and Women’s Hospital, and is also undertaking a PhD in renal cancer and the application of multi-omics profiling at the Institute for Molecular Bioscience, The University of Queensland.

• Pham, Duy Truong, The University of Queensland, Saint Lucia, Queensland, Australia

Duy Truong Pham,

• Tan, Xiao, The University of Queensland, Saint Lucia, Queensland, Australia

Xiao Tan,

• Grice, Laura F., The University of Queensland, Saint Lucia, Queensland, Australia

Laura F. Grice,

• Lam, Pui Yeng, The University of Queensland, Saint Lucia, Queensland, Australia

Pui Yeng Lam,

• Crawford, Joanna, The University of Queensland, Saint Lucia, Queensland, Australia

Joanna Crawford,

• Andersen, Stacey, The University of Queensland, Saint Lucia, Queensland, Australia

Stacey Andersen,

• Yoon, Sohye, The University of Queensland, Saint Lucia, Queensland, Australia

Sohye Yoon,

• Holland, Samuel Edward, The University of Queensland, Saint Lucia, Queensland, Australia

Samuel Edward Holland,

• Francis, Leo, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Leo Francis,

• Combes, Alexander N., Monash University Monash Biomedicine Discovery Institute, Clayton, Victoria, Australia

Alexander N. Combes,

• Kassianos, Andrew J., Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Andrew J. Kassianos,

• Healy, Helen G., Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Helen G. Healy,

• Nguyen, Quan, The University of Queensland Institute for Molecular Bioscience, Saint Lucia, Queensland, Australia

Quan Nguyen,

• Mallett, Andrew John, Royal Brisbane and Women's Hospital, Herston, Queensland, Australia

Andrew John Mallett,

Background

Advances in sequencing methods have increased available molecular information on dissociated cells and tissues. Spatially linking this molecular information with histomorphology is needed to understand a complex organ like the kidney, in both health and disease.

Methods

Here we used the commercially available 10x Genomics ST platform to investigate the spatially resolved transcriptome expressions in fetal (n=2), adult male (n=3) and female (n=3) mouse frozen kidney and a healthy human cortical frozen kidney tissue sections. We utilised Space Ranger (10x Genomics), Seurat and stLearn analysis pipelines to explore the spatial transcriptome expression within the kidney tissue sections. Furthermore, we confirmed the robustness of our ST data against matched publicly available mouse and human kidney scRNA-seq data.

Results

We identified a unique transcriptome plasticity in fetal and adult mouse kidneys, and healthy human cortical kidney tissue. Further dimensional reduction identified transcriptome clusters which correlated with distinct developing kidney structures in fetal mouse kidney tissue, functional cortical and medulla regions in adult mouse kidney tissue, and scarred and non-scarred regions in human cortical kidney tissue.

Conclusion

ST is a non-dissociative sequencing and imaging method which allows molecular profiles to be integrated with histomorphology of frozen kidney tissue sections. This provides a novel opportunity to inform physiological and non-physiological conditions at the cell-cell, nephron and tissue levels.

ST provides transcriptome expression within intact kideny tissue sections. (A) H&E stained human cortical kidney tissue with scarred and non-scarred regions. (B) The same human cortical kidney tissue with the transcript capture spots coloured by clustering using t-SNE projection demonstrates distinct transcriptome expression in scarred and non-scarred regions.

Funding

• Government Support - Non-U.S.