Evidence map›Paper›PMID 26493500›Full record

ArticleNature communications2015

Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.

Benjamin S Freedman, Craig R Brooks, Albert Q Lam, Hongxia Fu, Ryuji Morizane, Vishesh Agrawal, Abdelaziz F Saad, Michelle K Li, Michael R Hughes, Ryan Vander Werff and 11 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 441 papers.

0numbers the graph read from it
0cells of the map it votes in
441citing papers in PubMed
25.5field-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

441 citing papers in PubMed, 761 citations in OpenAlex.

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  19. Deciphering the Impact of RAC1-SPTAN1 in ARPKD Cystogenesis Using Multifaceted Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Article

381 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 3 institutions in 2 countries.

Benjamin S FreedmanDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Craig R BrooksDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Albert Q LamDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Hongxia FuDepartment of Biological Chemistry and Pharmacology, Boston Children's Hospital, Center for Life Sciences, Harvard Medical School, Room 3103, 3 Blackfan Circle, Boston, Massachusetts 02115, USA.
Ryuji MorizaneDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Vishesh AgrawalDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 823, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Abdelaziz F SaadDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Michelle K LiDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Michael R HughesThe Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Ryan Vander WerffThe Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Derek T PetersDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild Biochemistry Building 160, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Junjie LuDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 823, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Anna BacceiDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 823, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Andrew M SiedleckiDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
M Todd ValeriusDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Kiran MusunuruDepartment of Stem Cell and Regenerative Biology, Harvard University, Sherman Fairchild Biochemistry Building 160, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Kelly M McNagnyThe Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Theodore I SteinmanDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Jing ZhouDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Paul H LerouHarvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Joseph V BonventreDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard Institutes of Medicine Suite 550, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Brigham and Women's Hospital · USUniversity of British Columbia · CABoston Children's Hospital · US

Funding

KIDNEY INJURY MOLECULE-1 IN EPITHELIAL REPAIRR01DK072381 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2005 to 2025
$8.6M
Mechanisms of Ischemic Kidney Injury and RepairR01DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JOSEPH VINCENT BONVENTRE · 1987 to 2026
$6.2M
Mechanisms of Ischemic Kidney Injury and RepairR37DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 1993 to 2021
$5.2M
Mouse model of polycystic kidney diseaseR37DK051050 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHOU, JING · 2005 to 2014
$4.2M
MODEL OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASER01DK051050 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHOU, JING · 1995 to 2004
$2.0M
Harvard Summer Research Program in Kidney MedicineR25DK101398 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI JOSEPH VINCENT BONVENTRE · 2014 to 2026
$1.5M
Cell biology of autosomal dominant polycystic kidney diseaseR01DK099532 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI ZHOU, JING · 2014 to 2016
$796k
THE ROLE OF REGULATOR OF G-PROTEIN SIGNALING 4 IN ACUTE KIDNEY INJURYK08DK089002 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SIEDLECKI, ANDREW MICHAEL · 2011 to 2015
$795k
Proximal tubule Kim-1 expression modulates acute and chronic kidney injuryK01DK099473 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROOKS, CRAIG ROBERT · 2013 to 2017
$787k
Modeling Polycystic Kidney Disease Using Human Induced Pluripotent Stem CellsK01DK102826 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2014 to 2018
$743k
Modeling Polycystic Kidney Disease Using Human Induced Pluripotent Stem CellsF32DK092036 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI FREEDMAN, BENJAMIN SOLOMON · 2011 to 2013
$174k
CIHR MOP-84545NIDDK NIH HHS DK072381NIDDK NIH HHS DK092036NIDDK NIH HHS DK099532NIDDK NIH HHS DK102826NIDDK NIH HHS DK39773NIDDK NIH HHS DK51050NIDDK NIH HHS DK864406NIDDK NIH HHS F32 DK092036NIDDK NIH HHS K01 DK099473NIDDK NIH HHS K01 DK102826NIDDK NIH HHS K08 DK089002NIDDK NIH HHS R01 DK039773NIDDK NIH HHS R01 DK051050NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R01 DK099532NIDDK NIH HHS R25 DK101398NIDDK NIH HHS R37 DK039773NIDDK NIH HHS R37 DK051050
6 · The paper itself

Abstract

Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications.

Indexed as

Cell DifferentiationClustered Regularly Interspaced Short Palindromic RepeatsEmbryonic Stem CellsGene Knockout TechniquesGerm LayersHumansKidneyKidney DiseasesModels, BiologicalOrganoidsPluripotent Stem CellsSialoglycoproteinspodocalyxinSialoglycoproteins

Identifiers

PMID26493500
PMCPMC4620584
OpenAlexW2176166968

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.