Evidence map›Paper›PMID 40503936›Full record

ArticleCell reports2025

Lysophosphatidic acid and sphingosine-1-phosphate are apical polarity cues in multiple organoid systems.

Andrew M Tidball, Jinghui Luo, J Clayton Walker, Charlotte Y Yang, Keithan Lee, Ryan C Spencer, Carissa Matthews, Geshan Feng, Peggy P Hsu, Yusoo Lee and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Multiscale imaging of polarity in bovine oviductal organoids.Frontiers in cell and developmental biology · 2026
    Article
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

15 authors.

Andrew M TidballDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: atidball@umich.edu.
Jinghui LuoDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
J Clayton WalkerDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Charlotte Y YangDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Keithan LeeDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ryan C SpencerDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Carissa MatthewsDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Geshan FengDepartment of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Peggy P HsuDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Yusoo LeeDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Jack MorganDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Charlie J ChildsDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Madeline K EikenDepartment of Biomedical Engineering, University of Michigan Medical School and University of Michigan College of Engineering, Ann Arbor, MI, USA.
Katherine D WaltonDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Jason R SpenceDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan Medical School and University of Michigan College of Engineering, Ann Arbor, MI, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.

Funding

Michigan Institute for Clinical and Health Research (MICHR)UM1TR004404 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Julie C Lumeng · 2023 to 2026
$39.8M
Understanding Genetic Complexity in Spina BifidaR01HD111089 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI RICHARD H. FINNELL, MARGARET ELIZABETH ROSS · 2023 to 2026
$2.8M
Human iPSC intestine mimetics with integrated mesenchymal, endothelial and enteric nervous tissueR01DK137806 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason Spence · 2024 to 2026
$1.5M
Modeling genetic anencephaly with human brain organoidsR03HD104901 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TIDBALL, ANDREW M · 2022 to 2023
$248k
NCATS NIH HHS UM1 TR004404NICHD NIH HHS R01 HD111089NICHD NIH HHS R03 HD104901NIDDK NIH HHS R01 DK137806
6 · The paper itself

Abstract

Apicobasal polarization is crucial for tissue organization during in vivo development and in human organoid models. Extracellular matrix (ECM) signaling typically provides a basal cue, and intestinal and lung organoids reverse polarity from apical-in to apical-out after ECM removal. However, ECM-free brain organoids maintain apical-in polarity, suggesting that media components may influence polarity. Exposing brain organoids to serum induced apical-out orientation. Lysophosphatidic acid (LPA), present in the medium of prior apical-out techniques, was identified as the causative factor. LPA-induced apical-out orientation in brain organoids occurred within 1 day, lasted at least 1 month, and was optimal at human cerebrospinal fluid LPA concentrations. Sphingosine-1-phosphate (S1P) induced similar apical-out polarization. Pharmacological studies revealed that LPA/S1P act via a G-protein coupled receptor/RhoA pathway. Finally, LPA induced apical-out polarity in patient-derived human lung and intestinal organoids, iPSC spheres, and multilineage iPSC-derived intestinal organoids. These findings indicate that LPA signaling is a critical apical polarity cue in multiple tissues.

Indexed as

Cell PolarityLysophospholipidsOrganoidsSphingosineBrainExtracellular MatrixHumansInduced Pluripotent Stem CellsLungrhoA GTP-Binding ProteinSignal Transductionlysophosphatidic acidLysophospholipidsrhoA GTP-Binding ProteinSphingosinesphingosine 1-phosphateapical-outapicobasal polaritybrain organoidcerebrospinal fluidCP: Cell biologyCP: Stem cell researchepitheliumLPAR1phospholipid signalingRhotight junctions

Identifiers

PMID40503936
PMCPMC12315026

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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.