Evidence map›Paper›PMID 24357672›Full record

ArticleJournal of the American Society of Nephrology : JASN2014

Rapid and efficient differentiation of human pluripotent stem cells into intermediate mesoderm that forms tubules expressing kidney proximal tubular markers.

Albert Q Lam, Benjamin S Freedman, Ryuji Morizane, Paul H Lerou, M Todd Valerius, Joseph V Bonventre

Abstract read
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed
14.1field-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

158 citing papers in PubMed, 308 citations in OpenAlex.

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  18. Kidney Disease Modeling with Organoids and Organs-on-Chips.Annual review of biomedical engineering · 2024
    Review
  19. NAT10-mediated acCell proliferation · 2024
    Article
  20. Review

98 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

6 authors at 4 institutions in 3 countries.

Albert Q LamRenal Division, Department of Medicine, and Harvard Stem Cell Institute, Cambridge, Massachusetts; and aqlam@partners.org.
Benjamin S FreedmanRenal Division, Department of Medicine, and Harvard Stem Cell Institute, Cambridge, Massachusetts; and.
Ryuji MorizaneRenal Division, Department of Medicine, and Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Paul H LerouHarvard Stem Cell Institute, Cambridge, Massachusetts; and Department of Newborn Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
M Todd ValeriusRenal Division, Department of Medicine, and Harvard Stem Cell Institute, Cambridge, Massachusetts; and.
Joseph V BonventreRenal Division, Department of Medicine, and Harvard Stem Cell Institute, Cambridge, Massachusetts; and.
Metabolism and Renal Physiology · FRBrigham and Women's Hospital · USHarvard Stem Cell Institute · USKeio University · JP

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
INDUCIBLE PLURIPOTENT STEM CELLS AND KIDNEY REGENERATIONRC1DK086406 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2009 to 2010
$995k
Genomic stability of human pluripotent stem cellsR00HD061981 · NICHD · BRIGHAM AND WOMEN'S HOSPITAL · PI LEROU, PAUL HUBERT · 2011 to 2013
$710k
Modeling Polycystic Kidney Disease Using Human Induced Pluripotent Stem CellsF32DK092036 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI FREEDMAN, BENJAMIN SOLOMON · 2011 to 2013
$174k
Differentiation of Human iPS Cells into Kidney Proximal Tubular CellsF32DK084692 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI LAM, ALBERT · 2009 to 2011
$74k
NICHD NIH HHS R00 HD061981NICHD NIH HHS R00HD061981NIDDK NIH HHS F32 DK084692NIDDK NIH HHS F32DK084692NIDDK NIH HHS F32 DK092036NIDDK NIH HHS R01 DK039773NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R01DK39773NIDDK NIH HHS R37 DK039773NIDDK NIH HHS RC1 DK086406NIDDK NIH HHS RC1DK0864406
6 · The paper itself

Abstract

Human pluripotent stem cells (hPSCs) can generate a diversity of cell types, but few methods have been developed to derive cells of the kidney lineage. Here, we report a highly efficient system for differentiating human embryonic stem cells and induced pluripotent stem cells (referred to collectively as hPSCs) into cells expressing markers of the intermediate mesoderm (IM) that subsequently form tubule-like structures. Treatment of hPSCs with the glycogen synthase kinase-3β inhibitor CHIR99021 induced BRACHYURY(+)MIXL1(+) mesendoderm differentiation with nearly 100% efficiency. In the absence of additional exogenous factors, CHIR99021-induced mesendodermal cells preferentially differentiated into cells expressing markers of lateral plate mesoderm with minimal IM differentiation. However, the sequential treatment of hPSCs with CHIR99021 followed by fibroblast growth factor-2 and retinoic acid generated PAX2(+)LHX1(+) cells with 70%-80% efficiency after 3 days of differentiation. Upon growth factor withdrawal, these PAX2(+)LHX1(+) cells gave rise to apically ciliated tubular structures that coexpressed the proximal tubule markers Lotus tetragonolobus lectin, N-cadherin, and kidney-specific protein and partially integrated into embryonic kidney explant cultures. With the addition of FGF9 and activin, PAX2(+)LHX1(+) cells specifically differentiated into cells expressing SIX2, SALL1, and WT1, markers of cap mesenchyme nephron progenitor cells. Our findings demonstrate the effective role of fibroblast growth factor signaling in inducing IM differentiation in hPSCs and establish the most rapid and efficient system whereby hPSCs can be differentiated into cells with features characteristic of kidney lineage cells.

Indexed as

AnimalsAntineoplastic AgentsBiomarkersCell DifferentiationCell LineFemaleFibroblast Growth Factor 2FibroblastsForeskinGlycogen Synthase Kinase 3HumansKidney Tubules, ProximalLIM-Homeodomain ProteinsMaleMesodermMiceAntineoplastic AgentsBiomarkersChir 99021Fibroblast Growth Factor 2Glycogen Synthase Kinase 3LHX1 protein, humanLhx1 protein, mouseLIM-Homeodomain ProteinsPAX2 protein, humanPax2 protein, mousePAX2 Transcription FactorPyridinesPyrimidinesTranscription FactorsTretinoin

Identifiers

PMID24357672
PMCPMC4033376
OpenAlexW2103565029

What OpenQuestion holds

Textmetadata
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.