Evidence map›Paper›PMID 34591094›Full record

ArticleBiology of reproduction2022

Single-cell analysis of prostaglandin E2-induced human decidual cell in vitro differentiation: a minimal ancestral deciduogenic signal†.

Daniel J Stadtmauer, Günter P Wagner

Open access · greenAbstract read
In one paragraph

Article in Biology of reproduction, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Disruption of primary ciliary prostaglandin EJournal of biomedical science · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. TNFSF14The EMBO journal · 2024
    Article
  13. Article
  14. The Role of the Endometrium in Implantation: A Modern View.International journal of molecular sciences · 2024
    Review
  15. Article
  16. Article
  17. Article
  18. Frontiers in immunology · 2024
    Article
  19. Review
  20. 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

2 authors at 1 institution in 1 country.

Daniel J Stadtmauer
Günter P Wagner
Yale University · US

Funding

PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Systems analysis of phenotypic switch in control of cancer invasionU54CA209992 · NCI · YALE UNIVERSITY · PI LEVCHENKO, ANDRE · 2016 to 2021
$10.1M
NCI NIH HHS U54 CA209992NIGMS NIH HHS T32 GM007499
6 · The paper itself

Abstract

The decidua is a hallmark of reproduction in many placental mammals. Differentiation of decidual stromal cells is known to be induced by progesterone and the cyclic AMP/protein kinase A (cAMP/PKA) pathway. Several candidates have been identified as the physiological stimulus for adenylyl cyclase activation, but their relative importance remains unclear. To bypass this uncertainty, the standard approach for in vitro experiments uses membrane-permeable cAMP and progestin. We phylogenetically infer that prostaglandin E2 (PGE2) likely was the signal that ancestrally induced decidualization in conjunction with progesterone. This suggests that PGE2 and progestin should be able to activate the core gene regulatory network of decidual cells. To test this prediction, we performed a genome-wide study of gene expression in human endometrial fibroblasts decidualized with PGE2 and progestin. Comparison to a cAMP-based protocol revealed shared activation of core decidual genes and decreased induction of senescence-associated genes. Single-cell transcriptomics of PGE2-mediated decidualization revealed a distinct, early-activated state transitioning to a differentiated decidual state. PGE2-mediated decidualization was found to depend upon progestin-dependent induction of PGE2 receptor 2 (PTGER2) which in turn leads to PKA activation upon PGE2 stimulation. Progesterone-dependent induction of PTGER2 is absent in opossum, an outgroup taxon of placental mammals which is incapable of decidualization. Together, these findings suggest that the origin of decidualization involved the evolution of progesterone-dependent activation of the PGE2/PTGER2/PKA axis, facilitating entry into a PKA-dominant rather than AKT-dominant cellular state. We propose the use of PGE2 for in vitro decidualization as an alternative to 8-Br-cAMP.

Indexed as

Cell DifferentiationCell Line, TransformedCells, CulturedCyclic AMPCyclic AMP-Dependent Protein KinasesDeciduaDinoprostoneEndometriumFemaleFibroblastsGene ExpressionGenome-Wide Association StudyHumansMedroxyprogesterone AcetatePregnancyReceptors, Prostaglandin E, EP2 SubtypeCyclic AMPCyclic AMP-Dependent Protein KinasesDinoprostoneMedroxyprogesterone AcetatePTGER2 protein, humanReceptors, Prostaglandin E, EP2 Subtypecell type originationdeciduadecidual stromal cellendometrial stromal fibroblastevolution of mammalian pregnancyprostaglandin E2PTGER2senescence

Identifiers

PMID34591094
PMCPMC8757638
OpenAlexW3202714432

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.