PT  - JOURNAL ARTICLE
AU  - Ayshwarya Subramanian
AU  - Eriene-Heidi Sidhom
AU  - Maheswarareddy Emani
AU  - Nareh Sahakian
AU  - Katherine Vernon
AU  - Yiming Zhou
AU  - Maria Kost-Alimova
AU  - Astrid Weins
AU  - Michal Slyper
AU  - Julia Waldman
AU  - Danielle Dionne
AU  - Lan T Nguyen
AU  - Jamie Marshall
AU  - Orit Rosenblatt-Rosen
AU  - Aviv Regev
AU  - Anna Greka
TI  - Kidney organoid reproducibility across multiple human iPSC lines and diminished off target cells after transplantation revealed by single cell transcriptomics
AID  - 10.1101/516807
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 516807
4099  - http://biorxiv.org/content/early/2019/01/10/516807.short
4100  - http://biorxiv.org/content/early/2019/01/10/516807.full
AB  - Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we used single cell RNA-Seq (scRNA-Seq) to profile 415,775 cells to show that organoid composition and development are comparable to human fetal and adult kidneys. Although cell classes were largely reproducible across iPSC lines, time points, protocols, and replicates, cell proportions were variable between different iPSC lines. Off-target cell proportions were the most variable. Prolonged in vitro culture did not alter cell types, but organoid transplantation under the mouse kidney capsule diminished off-target cells. Our work shows how scRNA-seq can help score organoids for reproducibility, faithfulness and quality, that kidney organoids derived from different iPSC lines are comparable surrogates for human kidney, and that transplantation enhances their formation by diminishing off-target cells.