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ScoMorphoFISH: A deep learning enabled toolbox for single-cell single-mRNA quantification and correlative

Florian Siegerist1, Eleonora Hay1,2, Juan Saydou Dikou1

  • 1Institute for Anatomy and Cell Biology, University Medicine Greifswald, Greifswald, Germany.

Journal of Cellular and Molecular Medicine
|May 20, 2022
PubMed
Summary
This summary is machine-generated.

A new toolbox, scoMorphoFISH, enables spatial single-cell, single-mRNA analysis of kidney biopsies. This method links gene expression to morphology, improving diagnostics and research by revealing localized cellular changes.

Keywords:
SARS-CoV-2kidney biopsypodocyterenal pathologysuper-resolution microscopy

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Bioinformatics

Background:

  • Current kidney biopsy analysis separates mRNA and morphology, losing spatial and single-cell context.
  • Integrating molecular and structural data is crucial for advancing kidney disease research and personalized medicine.

Purpose of the Study:

  • To introduce scoMorphoFISH, a novel toolbox for spatial single-cell, single-mRNA expression analysis in kidney biopsies.
  • To correlate gene expression with cellular morphology at a high resolution within intact tissue.

Main Methods:

  • Development of scoMorphoFISH, a modular toolbox for spatial transcriptomics and morphometry.
  • Application of deep learning for virtual tissue dissection and cell type identification.
  • Super-resolution microscopy for detailed podocyte foot process morphometry.

Main Results:

  • scoMorphoFISH successfully integrates spatial single-cell mRNA data with detailed morphology.
  • The method identified local ACE2 upregulation in podocytes following injury.
  • ACE2 expression correlated with SARS-CoV-2 in a COVID-19-associated FSGS patient.

Conclusions:

  • scoMorphoFISH provides unprecedented spatial, single-cell resolution for kidney biopsy analysis.
  • This approach enhances the identification of localized molecular changes in rare cell types.
  • The toolbox is readily applicable to standard FFPE samples for immediate clinical and research use.