Evidence map›Paper›PMID 35978039›Full record

ReviewNature protocols2022

Directed differentiation of human pluripotent stem cells into diverse organ-specific mesenchyme of the digestive and respiratory systems.

Keishi Kishimoto, Kentaro Iwasawa, Alice Sorel, Carlos Ferran-Heredia, Lu Han, Mitsuru Morimoto, James M Wells, Takanori Takebe, Aaron M Zorn

Open access · greenAbstract readReview
In one paragraph

Review in Nature protocols, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Epithelial architecture and signaling activity in the adult human esophagus.Frontiers in cell and developmental biology · 2025
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Mesodermal Derivatives of Pluripotent Stem Cells Route to Scarless Healing.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Review
  20. 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

9 authors at 2 institutions in 3 countries.

Keishi KishimotoCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-2938-1754
Kentaro IwasawaCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
Alice SorelCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0001-7902-8986
Carlos Ferran-HerediaCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
Lu HanCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
Mitsuru MorimotoLaboratory for Lung Development and Regeneration, RIKEN Center for Biosystems Dynamics Research (BDR), Kobe, Japan.
James M WellsCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-1398-848X
Takanori TakebeCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-6989-3041
Aaron M ZornCenter for Stem Cell and Organoid Medicine (CuSTOM), Perinatal Institute, Division of Developmental Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA. aaron.zorn@cchmc.org.ORCID http://orcid.org/0000-0003-3217-3590
Cincinnati Children's Hospital Medical Center · USTokyo Medical and Dental University · JP

Funding

Project-3: Modeling EA/TEF in human organoidsP01HD093363 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI Aaron M Zorn · 2017 to 2026
$16.2M
Engineering multi-organs in a dishDP2DK128799 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI TAKEBE, TAKANORI · 2020 to 2020
$2.3M
NICHD NIH HHS P01 HD093363NIDDK NIH HHS DP2 DK128799
6 · The paper itself

Abstract

Development of visceral organs such as the esophagus, lung, liver and stomach are coordinated by reciprocal signaling interactions between the endoderm and adjacent mesoderm cells in the fetal foregut. Although the recent successes in recapitulating developmental signaling in vitro has enabled the differentiation of human pluripotent stem cells (hPSCs) into various types of organ-specific endodermal epithelium, the generation of organ-specific mesenchyme has received much less attention. This is a major limitation in ongoing efforts to engineer complex human tissue. Here, we describe a protocol to differentiate hPSCs into different types of organ-specific mesoderm, leveraging signaling networks and molecular markers elucidated from single-cell transcriptomics of mouse foregut organogenesis. Building on established methods, hPSC-derived lateral plate mesoderm treated with either retinoic acid (RA) or RA together with a Hedgehog (HH) agonist generates posterior or anterior foregut splanchnic mesoderm, respectively, after 4-d cultures. These are directed into organ-specific mesenchyme lineages by the combinatorial activation or inhibition of WNT, BMP, RA or HH pathways from days 4 to 7 in cultures. By day 7, the cultures are enriched for different types of mesoderm with distinct molecular signatures: 60-90% pure liver septum transversum/mesothelium-like, 70-80% pure liver-like fibroblasts and populations of ~35% respiratory-like mesoderm, gastric-like mesoderm or esophageal-like mesoderm. This protocol can be performed by anyone with moderate experience differentiating hPSCs, provides a novel platform to study human mesoderm development and can be used to engineer more complex foregut tissue for disease modeling and regenerative medicine.

Indexed as

Hedgehog ProteinsPluripotent Stem CellsAnimalsCell DifferentiationEndodermHumansLungMesodermMiceTretinoinHedgehog ProteinsTretinoin

Identifiers

PMID35978039
PMCPMC9633385
OpenAlexW4292121815

What OpenQuestion holds

Textmetadata
LicenceTDM
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.