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Organoid single cell profiling identifies a transcriptional signature of glomerular disease.

Publication ,  Journal Article
Harder, JL; Menon, R; Otto, EA; Zhou, J; Eddy, S; Wys, NL; O'Connor, C; Luo, J; Nair, V; Cebrian, C; Spence, JR; Bitzer, M; Troyanskaya, OG ...
Published in: JCI Insight
January 10, 2019

Podocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte injury and compensation mechanisms are challenging to analyze in vivo. Human kidney organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease and regeneration, present an opportunity to explore the transcriptional plasticity of podocytes. Here, transcriptional profiling of more than 12,000 single cells from human PSC-derived kidney organoid cultures was used to identify robust and reproducible cell lineage gene expression signatures shared with developing human kidneys based on trajectory analysis. Surprisingly, the gene expression signature characteristic of developing glomerular epithelial cells was also observed in glomerular tissue from a kidney disease cohort. This signature correlated with proteinuria and inverse eGFR, and it was confirmed in an independent podocytopathy cohort. Three genes in particular were further characterized as potentially novel components of the glomerular disease signature. We conclude that cells in human PSC-derived kidney organoids reliably recapitulate the developmental transcriptional program of podocytes and other cell lineages in the human kidney and that transcriptional profiles seen in developing podocytes are reactivated in glomerular disease. Our findings demonstrate an approach to identifying potentially novel molecular programs involved in the pathogenesis of glomerulopathies.

Duke Scholars

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 10, 2019

Volume

4

Issue

1

Location

United States

Related Subject Headings

  • Transcriptome
  • Tissue Culture Techniques
  • Single-Cell Analysis
  • Podocytes
  • Pluripotent Stem Cells
  • Organoids
  • Kidney Glomerulus
  • Kidney Diseases
  • Humans
  • Embryonic Stem Cells
 

Citation

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Harder, J. L., Menon, R., Otto, E. A., Zhou, J., Eddy, S., Wys, N. L., … Nephrotic Syndrome Study Network (NEPTUNE), . (2019). Organoid single cell profiling identifies a transcriptional signature of glomerular disease. JCI Insight, 4(1). https://doi.org/10.1172/jci.insight.122697
Harder, Jennifer L., Rajasree Menon, Edgar A. Otto, Jian Zhou, Sean Eddy, Noel L. Wys, Christopher O’Connor, et al. “Organoid single cell profiling identifies a transcriptional signature of glomerular disease.JCI Insight 4, no. 1 (January 10, 2019). https://doi.org/10.1172/jci.insight.122697.
Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, et al. Organoid single cell profiling identifies a transcriptional signature of glomerular disease. JCI Insight. 2019 Jan 10;4(1).
Harder, Jennifer L., et al. “Organoid single cell profiling identifies a transcriptional signature of glomerular disease.JCI Insight, vol. 4, no. 1, Jan. 2019. Pubmed, doi:10.1172/jci.insight.122697.
Harder JL, Menon R, Otto EA, Zhou J, Eddy S, Wys NL, O’Connor C, Luo J, Nair V, Cebrian C, Spence JR, Bitzer M, Troyanskaya OG, Hodgin JB, Wiggins RC, Freedman BS, Kretzler M, European Renal cDNA Bank (ERCB), Nephrotic Syndrome Study Network (NEPTUNE). Organoid single cell profiling identifies a transcriptional signature of glomerular disease. JCI Insight. 2019 Jan 10;4(1).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

January 10, 2019

Volume

4

Issue

1

Location

United States

Related Subject Headings

  • Transcriptome
  • Tissue Culture Techniques
  • Single-Cell Analysis
  • Podocytes
  • Pluripotent Stem Cells
  • Organoids
  • Kidney Glomerulus
  • Kidney Diseases
  • Humans
  • Embryonic Stem Cells