Evidence map›Paper›PMID 29779890›Full record

ArticleCell stem cell2018

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

Stefan M Czerniecki, Nelly M Cruz, Jennifer L Harder, Rajasree Menon, James Annis, Edgar A Otto, Ramila E Gulieva, Laura V Islas, Yong Kyun Kim, Linh M Tran and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 283 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
283citing papers in PubMed, 1 pooled it
19.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

283 citing papers in PubMed, 1 synthesis or guideline pooled it, 450 citations in OpenAlex.

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  13. Deciphering the Impact of RAC1-SPTAN1 in ARPKD Cystogenesis Using Multifaceted Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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223 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 1 country.

Stefan M CzernieckiDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Nelly M CruzDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Jennifer L HarderDepartment of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Rajasree MenonDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
James AnnisInstitute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Edgar A OttoDepartment of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ramila E GulievaDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Laura V IslasDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Yong Kyun KimDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Linh M TranDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Medicine, Division of Hematology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Timothy J MartinsInstitute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA.
Jeffrey W PippinDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Hongxia FuInstitute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Medicine, Division of Hematology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Matthias KretzlerDepartment of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Stuart J ShanklandDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Jonathan HimmelfarbDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA.
Randall T MoonInstitute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Pharmacology, University of Washington School of Medicine and Howard Hughes Medical Institute, Seattle, WA 98109, USA.
Neal ParagasDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Benjamin S FreedmanDepartment of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine and Quellos High Throughput Screening Core, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Pathology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address: benof@uw.edu.
University of Washington · USUniversity of Michigan–Ann Arbor · US

Funding

Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GIPSON, DEBBIE S · 2009 to 2023
$20.3M
Using iPSCs to model patient outcomes in nephrotic syndromeUH3TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2014 to 2016
$6.1M
Juxta-glomerular cells serve as glomerular epithelial cell progenitors in glomerular diseaseR01DK097598 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES, WESSELY, OLIVER · 2014 to 2022
$5.2M
A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUG3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2017 to 2018
$2.9M
A Tissue Engineered Human Kidney Microphysiological SystemUH2TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2012 to 2013
$2.1M
Mechanoregulatory mechanisms of von Willebrand disease and thrombosisK25HL135432 · NHLBI · UNIVERSITY OF WASHINGTON · PI FU, HONGXIA · 2017 to 2021
$890k
Genesis of Epithelial Cell LumensK08DK089119 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HARDER, JENNIFER L. · 2013 to 2017
$790k
Modeling Polycystic Kidney Disease Using Human Induced Pluripotent Stem CellsK01DK102826 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2014 to 2018
$743k
INTERCALATED CELLS OF THE DISTAL NEPHRON DEFEND THE URINARY SYSTEMR00DK094873 · NIDDK · UNIVERSITY OF WASHINGTON · PI PARAGAS, NEAL · 2015 to 2017
$732k
NCATS NIH HHS UG3 TR002158NCATS NIH HHS UH2 TR000504NCATS NIH HHS UH3 TR000504NHLBI NIH HHS K25 HL135432NIDDK NIH HHS K01 DK102826NIDDK NIH HHS K08 DK089119NIDDK NIH HHS R00 DK094873NIDDK NIH HHS R01 DK097598NIDDK NIH HHS U54 DK083912
6 · The paper itself

Abstract

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening.

Indexed as

Cell DifferentiationHigh-Throughput Screening AssaysPhenotypeAutomationCell Culture TechniquesHumansKidneyOrganoidsPluripotent Stem CellsSequence Analysis, RNA

Identifiers

PMID29779890
PMCPMC5984728
OpenAlexW2803499747

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.