Abstract: TH-PO572
Integration of Spatial Transcriptomics and Morphology in Assessing Atubular vs. Connected Glomeruli
Session Information
- Pathology and Lab Medicine
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1700 Pathology and Lab Medicine
Authors
- Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Deng, Ruining, Vanderbilt University, Nashville, Tennessee, United States
- Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Huo, Yuankai, Vanderbilt University, Nashville, Tennessee, United States
- Fogo, Agnes B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
We previously found that atubular glomeruli increased in mice with proximal tubule-specific injury compared to normal mice. We have developed AI algorithms to identify such atubular glomeruli from serial whole slide images (WSI) and also found subvisual morphologic features in 2D slides that could be detected by 3D AI. Using spatial transcriptomics, we aimed to assess the topography of gene expression and any correlation with morphologic alterations quantified by AI.
Methods
Wild-type (WT) and transgenic mice with tubular cell expression of the diphtheria toxin (DT) receptor were studied. All mice were injected with DT at week 0 and week 1 and sacrificed 6 weeks later. 19 serial sections from paraffin block tissue were cut, and all except the middle section were scanned for atubular glomeruli assessment by AI. The middle section was then used for spatial transcriptome. The morphologic features in the resulting 3D reconstructed atubular vs connected glomeruli were quantified by AI.
Results
Atubular glomerular were increased in DT vs WT mice (19.2% vs. 5.8%). The glomerular volume was increased, and the ratio of columnar to flat parietal epithelial cells (PECs) ratio was significantly decreased in atubular compared to connected glomeruli. Using spatial transcriptomic analysis, 412 differentially expressed genes were detected in atubular glomeruli in WT vs DT mice, while 6795 genes were differentially expressed comparing the connected glomeruli in WT vs DT mice. By comparing transcriptomics in atubular vs connected glomeruli in the same mouse, 170 differentially expressed genes were detected. Among them, genes related to extracellular matrix organization (such as DAG1, TIMP2), or related to cell migration (such as FLNA, MYLK) were upregulated.
Conclusion
Spatial transcriptomic sequencing complemented AI-assisted morphology assessment, uncovering potential mechanisms driving extracellular matrix organization, regulation of cell migration and PEC alterations in the pathogenesis of atubular glomeruli.
Funding
- NIDDK Support