Evidence map›Paper›PMID 41018120›Full record

ReviewHuman reproduction open2025

Generating human primordial germ cell-like cells from pluripotent stem cells: a scoping review of

Madalena Vaz Santos, Ilse J de Bruin, Nina Dartée, Mathangi Lakshmipathi, Geert Hamer, Callista L Mulder, Willy M Baarends, Ans M M Van Pelt, Susana M Chuva De Sousa Lopes

Abstract readReview
In one paragraph

Review in Human reproduction open, 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. Article
  2. Article
  3. Article
  4. Review
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.

Madalena Vaz SantosAmsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.
Ilse J de BruinDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.ORCID https://orcid.org/0000-0001-7459-089X
Nina DartéeDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.
Mathangi LakshmipathiAmsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.
Geert HamerAmsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.ORCID https://orcid.org/0000-0002-9583-6796
Callista L MulderAmsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.ORCID https://orcid.org/0000-0001-9160-7585
Willy M BaarendsDepartment of Developmental Biology, Erasmus MC, Rotterdam, The Netherlands.
Ans M M Van PeltAmsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands.
Susana M Chuva De Sousa LopesDepartment of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.ORCID https://orcid.org/0000-0003-3866-2803

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

study questionHow do the methods and outcomes of established protocols to specify human primordial germ cell-like cells (hPGCLCs) SUMMARY ANSWER: All analyzed protocols were successful in generating hPGCLCs, and a few were able to induce further germ cell maturation. WHAT IS KNOWN ALREADY: There are a variety of protocols for generating hPGCLCs STUDY DESIGN SIZE DURATION: For this scoping review, a systematic search for protocols was conducted in the databases Scopus and Web of Science, including publications since 2010. Search terms included human, differentiation/specification/induction, germ cell/oogonia/spermatogonia, and primordial. PARTICIPANTS/MATERIALS SETTING

methodsTwo separate authors performed the database search according to the inclusion/exclusion criteria. The data regarding the materials and methods as well as results of the included articles were extracted and organized based on protocol (cell type and culture system) and outcome. MAIN RESULTS AND THE ROLE OF CHANCE: A systematic search revealed 32 articles describing the generation of hPGCLCs. Of these, 24 articles contained an original hPGCLC differentiation protocol and 8 articles provided an extension of a previously published protocol. The extension protocols focused either on extending hPGCLC culture or maturing hPGCLCs further. The articles were compared regarding protocol methods and differentiation outcomes. The data showed that differentiation in 2D or 3D, in the presence of bone morphogenetic protein 4 (BMP4) (or retinoic acid), activated the WNT and NODAL signaling pathways to induce hPGCLCs. Further maturation (based on gene expression) was also achieved, depending on the inclusion of subsequent differentiation steps. The 2D culture systems showed high efficiency and scalability, while the 3D culture systems were more suitable for germ cell maturation purposes. Further improvements would include a deeper assessment of epigenetic and gene expression, functional analyses, and use of multiple cell lines to reflect protocol versatility. LIMITATIONS REASONS FOR CAUTION: Only literature has been compared; no extensive experimental comparison or a meta-analysis was performed due to the heterogeneity in outcome measurements. WIDER IMPLICATIONS OF THE

findingsThis review offers a comparison of hPGCLC differentiation protocols and aims to aid researchers in selecting appropriate protocols and making informed modifications to the culture conditions to achieve efficient germ cell differentiation. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMW (PSIDER 10250022120001) and by the Novo Nordisk Foundation (reNEW NNF21CC0073729). The authors declare no conflicts of interest. REGISTRATION NUMBER: N/A.

Indexed as

humanin vitro differentiationpluripotent stem cellsprimordial germ cell-like cellsprimordial germ cellsprotocol comparisons

Identifiers

PMID41018120
PMCPMC12472124

What OpenQuestion holds

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Registered trials

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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.