Evidence map›Paper›PMID 30096149›Full record

ArticlePLoS genetics2018

Transcription factor ASCL2 is required for development of the glycogen trophoblast cell lineage.

Aaron B Bogutz, Rosemary Oh-McGinnis, Karen J Jacob, Rita Ho-Lau, Ting Gu, Marina Gertsenstein, Andras Nagy, Louis Lefebvre

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  7. Review
  8. The multifaceted role of GCM1 during trophoblast differentiation in the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Article
  10. Article
  11. Article
  12. Disabling de novo DNA methylation in embryonic stem cells allows an illegitimate fate trajectory.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5-SN38 Antibody-drug Conjugate in Neuroendocrine Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  15. Article
  16. Article
  17. TEAD4 ensures postimplantation development by promoting trophoblast self-renewal: An implication in early human pregnancy loss.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. 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

8 authors at 2 institutions in 1 country.

Aaron B BogutzDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.
Rosemary Oh-McGinnisDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.
Karen J JacobDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.
Rita Ho-LauDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.
Ting GuDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.
Marina GertsensteinLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Andras NagyLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID 0000-0003-4311-0413
Louis LefebvreDepartment of Medical Genetics, Molecular Epigenetics Group, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0001-5664-9480
University of British Columbia · CAMount Sinai Hospital · CA

Funding

Canadian Institutes of Health Research MOP-119357Canadian Institutes of Health Research MOP-82863
6 · The paper itself

Abstract

The basic helix-loop-helix (bHLH) transcription factor ASCL2 plays essential roles in diploid multipotent trophoblast progenitors, intestinal stem cells, follicular T-helper cells, as well as during epidermal development and myogenesis. During early development, Ascl2 expression is regulated by genomic imprinting and only the maternally inherited allele is transcriptionally active in trophoblast. The paternal allele-specific silencing of Ascl2 requires expression of the long non-coding RNA Kcnq1ot1 in cis and the deposition of repressive histone marks. Here we show that Del7AI, a 280-kb deletion allele neighboring Ascl2, interferes with this process in cis and leads to a partial loss of silencing at Ascl2. Genetic rescue experiments show that the low level of Ascl2 expression from the paternal Del7AI allele can rescue the embryonic lethality associated with maternally inherited Ascl2 mutations, in a level-dependent manner. Despite their ability to support development to term, the rescued placentae have a pronounced phenotype characterized by severe hypoplasia of the junctional zone, expansion of the parietal trophoblast giant cell layer, and complete absence of invasive glycogen trophoblast cells. Transcriptome analysis of ectoplacental cones at E7.5 and differentiation assays of Ascl2 mutant trophoblast stem cells show that ASCL2 is required for the emergence or early maintenance of glycogen trophoblast cells during development. Our work identifies a new cis-acting mutation interfering with Kcnq1ot1 silencing function and establishes a novel critical developmental role for the transcription factor ASCL2.

Indexed as

Cell LineageAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationFemaleGene Expression Regulation, DevelopmentalGene SilencingGenomic ImprintingGenotyping TechniquesGlycogenHeterozygoteMaleMicePlacentaPregnancySequence Analysis, RNAAscl2 protein, mouseBasic Helix-Loop-Helix ProteinsGlycogen

Identifiers

PMID30096149
PMCPMC6105033
OpenAlexW2886227808

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.