Evidence map›Paper›PMID 32556644›Full record

ArticleJournal of gastroenterology2020

Retinoic acid receptor γ activation promotes differentiation of human induced pluripotent stem cells into esophageal epithelium.

Yasufumi Koterazawa, Michiyo Koyanagi-Aoi, Keiichiro Uehara, Yoshihiro Kakeji, Takashi Aoi

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Journal of gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

9 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Epithelial architecture and signaling activity in the adult human esophagus.Frontiers in cell and developmental biology · 2025
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Yasufumi KoterazawaDivision of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Michiyo Koyanagi-AoiDivision of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Keiichiro UeharaDivision of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Yoshihiro KakejiDivision of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Japan.
Takashi AoiDivision of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. takaaoi@med.kobe-u.ac.jp.
Kobe University · JPKobe University Hospital · JP

Funding

Japan Agency for Medical Research and Development 16817073Japan Agency for Medical Research and Development 17935556Japan Agency for Medical Research and Development 19203662Japan Society for the Promotion of Science 16673738Japan Society for the Promotion of Science 18958188Japan Society for the Promotion of Science 19K17490
6 · The paper itself

Abstract

backgroundThe esophagus is known to be derived from the foregut. However, the mechanisms regulating this process remain unclear. In particular, the details of the human esophagus itself have been poorly researched. In this decade, studies using human induced pluripotent stem cells (hiPSCs) have proven powerful tools for clarifying the developmental biology of various human organs. Several studies using hiPSCs have demonstrated that retinoic acid (RA) signaling promotes the differentiation of foregut into tissues such as lung and pancreas. However, the effect of RA signaling on the differentiation of foregut into esophagus remains unclear.

methodsWe established a novel stepwise protocol with transwell culture and an air-liquid interface system for esophageal epithelial cell (EEC) differentiation from hiPSCs. We then evaluated the effect of all-trans retinoic acid (ATRA), which is a retinoic acid receptor (RAR)α, RARβ and RARγ agonist, on the differentiation from the hiPSC-derived foregut. Finally, to identify which RAR subtype was involved in the differentiation, we used synthetic agonists and antagonists of RARα and RARγ, which are known to be expressed in esophagus.

resultsWe successfully generated stratified layers of cells expressing EEC marker genes that were positive for lugol staining. The enhancing effect of ATRA on EEC differentiation was clearly demonstrated with quantitative reverse transcription polymerase chain reaction, immunohistology, lugol-staining and RNA sequencing analyses. RARγ agonist and antagonist enhanced and suppressed EEC differentiation, respectively. RARα agonist had no effect on the differentiation.

conclusionWe revealed that RARγ activation promotes the differentiation of hiPSCs-derived foregut into EECs.

Indexed as

AnimalsCell DifferentiationCells, CulturedEpithelial CellsEsophagusHumansInduced Pluripotent Stem CellsMiceReceptors, Retinoic AcidRetinoic Acid Receptor alphaRetinoic Acid Receptor gammaReverse Transcriptase Polymerase Chain ReactionSignal TransductionTretinoinReceptors, Retinoic AcidRetinoic Acid Receptor alpharetinoic acid receptor betaRetinoic Acid Receptor gammaTretinoinEsophageal epithelial cell differentiationInduced pluripotent stem cellsRetinoic acid receptor γRetinoic acid signal

Identifiers

PMID32556644
PMCPMC7376085
OpenAlexW4231466723

What OpenQuestion holds

Textmetadata
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.