A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery

Copyright and License

© 2022 Elsevier Inc.

Acknowledgement

We appreciate the help from Dr. Andrew Ransick, Kari Koppitch, and Jinjin Guo with scRNA-seq sample preparation using 10X Genomics technology and validations, and members of the McMahon laboratory for insightful scientific discussions. We are grateful to the Choi family for their generous donation to establish the Choi Family Therapeutic Screening Center that enabled the small-molecule screens in this study and to Mickey Huang for assistance in the screening process. 

Funding

C.J.S. was supported by the Amgen-USC Postdoctoral Fellowship Program. T.T. was supported by the T32 Training Grant in Developmental Biology, Stem Cells and Regeneration from NICHD (T32HD060549). Work in A.P.M.’s laboratory was supported by a grant from NIDDK (DK054364).

Contributions

T.T., C.J.S., D.C.-H.L., and A.P.M. designed experiments. T.T., C.J.S., T.N., S.-Y.C., J.A.M., R.Y., B.D., S.Y.C., and N.O.L. performed the experiments, data collection and/or data analysis. T.T., C.J.S., and A.P.M. wrote the manuscript and incorporated collaborator, manuscript reviewer, and editorial inputs.

Conflict of Interest

A.P.M. receives consulting fees or stock options for his scientific advisory role for eGENESIS, TRESTLE BioTherapeutics, and IVIVA Medical. Amgen Inc. supports a USC-Amgen Scholar’s program, and C.J.S. is funded through this program. A.P.M., C.J.S., and T.T. have applied for intellectual property protection on work presented here (patent pending).

Supplemental Material

• Document S1. Figures S1–S7.
• Table S1. Differentially expressed gene lists that were used to identify clusters and for comparisons of in vitro and in vivo cell types, related to Figures 2, 3, S2, and S3. TPM values and GO terms from bulk RNA-seq analyses for various comparisons (related to Figures 7 and S7).
• Table S2. Annotated list of all PKI compounds used in the study, related to Figure 6.
• Table S3. gRNA and primer sequences used to generate and validate PKD1−/− and PKD2−/− hESC lines, related to Figures 5 and S5 and STAR Methods details.
• Document S2. Article plus supplemental information.