A Human Precision Cut Kidney Slice Platform for Studying Glomerular Biology and Therapeutic Responses
- 1University of Washington
Abstract
Introduction: Short term human precision cut kidney slice cultures (PCKS) represent a tractable experimental that contains mature kidney cell types within their native anatomic context and that can be manipulated in vitro. In this study, we employ genomic tools to analyze the PCKS response to culture conditions and their suitability for study of glomerular disease biology. Methods: The impact of culture medium and oxygenation on PCKS viability and gene expression was explored using spatial transcriptomics and traditional histologic approaches. The biological response of PCKS to IFN{gamma} stimulation and signaling suppression by the JAK1/2 inhibitor baricitinib were also explored. Results: A genome wide atlas of glomerular and tubulointerstitial gene expression patterns was generated from PCKS cultured in different media and oxygenation conditions and at various timepoints in culture. IFN{gamma} induced APOL1 gene and protein expression in glomeruli, which could be suppressed by baricitinib. Expression changes were reproducible in PCKS derived from multiple donors. Conclusions: PCKS are reproducibly responsive to IFN{gamma} stimulation, which will allow dissection of APOL1 mediated glomerular disease mechanisms in a human tissue model system. Spatial transcriptomic profiling of tissue responses helps to tailor culture medium/oxygenation to optimize the PCKS system to address specific biological questions.
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BibTeX
@misc{akilesh2026human,
title = {{A Human Precision Cut Kidney Slice Platform for Studying Glomerular Biology and Therapeutic Responses}},
author = {S. Akilesh and X. Li and B. Mills and C. Poudel and P. Vasquez and E. Beirne and J. C. Vaughan and K. D. Smith},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759734},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759734v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A Human Precision Cut Kidney Slice Platform for Studying Glomerular Biology and Therapeutic Responses
AU - S. Akilesh
AU - X. Li
AU - B. Mills
AU - C. Poudel
AU - P. Vasquez
AU - E. Beirne
AU - J. C. Vaughan
AU - K. D. Smith
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759734
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759734v1
AB - Introduction: Short term human precision cut kidney slice cultures (PCKS) represent a tractable experimental that contains mature kidney cell types within their native anatomic context and that can be manipulated in vitro. In this study, we employ genomic tools to analyze the PCKS response to culture conditions and their suitability for study of glomerular disease biology. Methods: The impact of culture medium and oxygenation on PCKS viability and gene expression was explored using spatial transcriptomics and traditional histologic approaches. The biological response of PCKS to IFN{gamma} stimulation and signaling suppression by the JAK1/2 inhibitor baricitinib were also explored. Results: A genome wide atlas of glomerular and tubulointerstitial gene expression patterns was generated from PCKS cultured in different media and oxygenation conditions and at various timepoints in culture. IFN{gamma} induced APOL1 gene and protein expression in glomeruli, which could be suppressed by baricitinib. Expression changes were reproducible in PCKS derived from multiple donors. Conclusions: PCKS are reproducibly responsive to IFN{gamma} stimulation, which will allow dissection of APOL1 mediated glomerular disease mechanisms in a human tissue model system. Spatial transcriptomic profiling of tissue responses helps to tailor culture medium/oxygenation to optimize the PCKS system to address specific biological questions.
ER -