Evidence map›Paper›PMID 33217324›Full record

ArticleStem cell reports2020

An In Vitro Differentiation Protocol for Human Embryonic Bipotential Gonad and Testis Cell Development.

Ingrid M Knarston, Svenja Pachernegg, Gorjana Robevska, Irene Ghobrial, Pei Xuan Er, Elizabeth Georges, Minoru Takasato, Alexander N Combes, Anne Jørgensen, Melissa H Little and 2 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

26 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Functional Validation of a Novel <italic>PBX1</italic> Missense Variant in a 46,XY Girl.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026
    Article
  6. Article
  7. In vitro models of the male reproductive system: applications for developmental and reproductive toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
  8. Review
  9. Article
  10. A new humanHuman reproduction open · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. A role for TRPC3 in mammalian testis development.Frontiers in cell and developmental biology · 2024
    Article
  18. Article
  19. Article
  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

12 authors at 5 institutions in 4 countries.

Ingrid M KnarstonMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Svenja PacherneggMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Gorjana RobevskaMurdoch Children's Research Institute, Melbourne, Australia.
Irene GhobrialMurdoch Children's Research Institute, Melbourne, Australia.
Pei Xuan ErMurdoch Children's Research Institute, Melbourne, Australia.
Elizabeth GeorgesMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Minoru TakasatoRIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Alexander N CombesMurdoch Children's Research Institute, Melbourne, Australia; Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia.
Anne JørgensenDepartment of Growth and Reproduction, Copenhagen University Hospital, Copenhagen, Denmark.
Melissa H LittleMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Australia.
Andrew H SinclairMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia.
Katie L AyersMurdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, The University of Melbourne, Melbourne, Australia. Electronic address: katie.ayers@mcri.edu.au.
The University of Melbourne · AUMurdoch Children's Research Institute · AUCopenhagen University Hospital · DKDiscovery Institute · USRIKEN Center for Biosystems Dynamics Research · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Currently an in vitro model that fully recapitulates the human embryonic gonad is lacking. Here we describe a fully defined feeder-free protocol to generate early testis-like cells with the ability to be cultured as an organoid, from human induced pluripotent stem cells. This stepwise approach uses small molecules to mimic embryonic development, with upregulation of bipotential gonad markers (LHX9, EMX2, GATA4, and WT1) at day 10 of culture, followed by induction of testis Sertoli cell markers (SOX9, WT1, and AMH) by day 15. Aggregation into 3D structures and extended culture on Transwell filters yielded organoids with defined tissue structures and distinct Sertoli cell marker expression. These studies provide insight into human gonadal development, suggesting that a population of precursor cells may originate from a more lateral region of the mesoderm. Our protocol represents a significant advance toward generating a much-needed human gonad organoid for studying disorders/differences of sex development.

Indexed as

Cell DifferentiationAntigens, DifferentiationEmbryo, MammalianHumansMaleSertoli CellsTissue Culture TechniquesAntigens, Differentiationdifferences in sex developmentdisorders of sex developmentDSDembryonic developmentgonadgonadal developmenthuman induced pluripotent stem cellsorganoid culturestem cell differentiationtestis

Identifiers

PMID33217324
PMCPMC7724470
OpenAlexW3100505853

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.