Evidence map›Paper›PMID 31600526›Full record

ArticleReproductive toxicology (Elmsford, N.Y.)2020

Molecular characterization of a toxicological tipping point during human stem cell differentiation.

Katerine S Saili, Todor Antonijevic, Todd J Zurlinden, Imran Shah, Chad Deisenroth, Thomas B Knudsen

Abstract read
In one paragraph

Article in Reproductive toxicology (Elmsford, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Use of computational toxicology tools to predictCurrent research in toxicology · 2022
    Article
  8. Article
  9. Chlorpyrifos and ΔCurrent research in toxicology · 2021
    Review
  10. Review
  11. Article
  12. Article
  13. 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

6 authors.

Katerine S SailiNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States.
Todor AntonijevicNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37830, United States; ToxStrategies, Katy, TX 77494, United States.
Todd J ZurlindenNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States.
Imran ShahNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States.
Chad DeisenrothNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States.
Thomas B KnudsenNational Center for Computational Toxicology (NCCT), U.S. Environmental Protection Agency, Office of Research & Development, 109 T.W. Alexander Drive, Research Triangle Park, NC 27711, United States. Electronic address: knudsen.thomas@epa.gov.

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

Endoderm gives rise to the gut tube in the early embryo. We differentiated human induced pluripotent stem cells (hiPSCs) to embryonic endoderm to identify a "tipping point" at which the developing system did not recover from perturbations caused by exposure to all-trans retinoic acid (ATRA). Differentiating hiPSC-derived endoderm exposed to five concentrations of ATRA between 0.001 and 10 μM at 6 h, 96 h, or 192 h was assessed for forkhead box A2 (FOXA2) protein expression and global gene transcript expression. A tipping point of 17 ± 11 nM was identified where patterns of differentially expressed genes supported a developmental trajectory shift indicating a potential teratogenic outcome. This concentration is between women's endogenous ATRA blood plasma levels and teratogenic levels of circulating isotretinoin, an ATRA isomer used to treat acne. Taken together, these data suggest that this approach is a sensitive method to identify a point of departure for chemicals that impact early embryonic development.

Indexed as

Cell DifferentiationCell LineGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsTeratogensTretinoinTeratogensTretinoinAll-trans retinoic acidDifferentiationEndodermEOMESFOXA2iPSCSOX17Tipping point

Identifiers

PMID31600526
PMCPMC9728154

What OpenQuestion holds

Textmetadata
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.