Evidence map›Paper›PMID 35064075›Full record

ArticleLife science alliance2022

Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells.

Johanna Grinat, Frauke Kosel, Neha Goveas, Andrea Kranz, Dimitra Alexopoulou, Klaus Rajewsky, Michael Sigal, A Francis Stewart, Julian Heuberger

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
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  5. Review
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  8. Prenatal stress induces changes in PAR2- and M3-dependent regulation of colon primitive cells.American journal of physiology. Gastrointestinal and liver physiology · 2022
    Article
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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 at 4 institutions in 1 country.

Johanna GrinatCancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Society, Berlin, Germany.ORCID 0000-0003-0152-4941
Frauke KoselCancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Society, Berlin, Germany.
Neha GoveasGenomics, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-2531-5514
Andrea KranzGenomics, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-7481-0220
Dimitra AlexopoulouDRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany.ORCID 0000-0002-3715-1756
Klaus RajewskyCancer Research Program, Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Society, Berlin, Germany.ORCID 0000-0002-6633-6370
Michael SigalMedical Department, Division of Gastroenterology and Hepatology, Charité University Medicine, Berlin, Germany.
A Francis StewartGenomics, Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
Julian HeubergerMedical Department, Division of Gastroenterology and Hepatology, Charité University Medicine, Berlin, Germany julian.heuberger@charite.de.ORCID 0000-0001-7205-732X
Max Delbrück Center · DETechnische Universität Dresden · DECenter for Systems Biology Dresden · DEMax Planck Institute of Molecular Cell Biology and Genetics · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Differentiation and lineage specification are controlled by cooperation of growth factor signalling. The involvement of epigenetic regulators in lineage specification remains largely elusive. Here, we show that the histone methyltransferase Mll1 prevents intestinal progenitor cells from differentiation, whereas it is also involved in secretory lineage specification of Paneth and goblet cells. Using conditional mutagenesis in mice and intestinal organoids, we demonstrate that loss of Mll1 renders intestinal progenitor cells permissive for Wnt-driven secretory differentiation. However, Mll1-deficient crypt cells fail to segregate Paneth and goblet cell fates. Mll1 deficiency causes Paneth cell-determined crypt progenitors to exhibit goblet cell features by unleashing Mapk signalling, resulting in increased numbers of mixed Paneth/goblet cells. We show that loss of Mll1 abolishes the pro-proliferative effect of Mapk signalling in intestinal progenitor cells and promotes Mapk-induced goblet cell differentiation. Our data uncover Mll1 and its downstream targets Gata4/6 as a regulatory hub of Wnt and Mapk signalling in the control of lineage specification of intestinal secretory Paneth and goblet cells.

Indexed as

AnimalsCell DifferentiationEpigenesis, GeneticEpigenomicsFemaleGoblet CellsHumansIntestinal MucosaIntestinesMaleMAP Kinase Signaling SystemMiceMice, TransgenicOrganoidsPaneth CellsStem Cells

Identifiers

PMID35064075
PMCPMC8807877
OpenAlexW4206902146

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.