Evidence map›Paper›PMID 29285667›Full record

ArticleStem cell reviews and reports2018

Epigenetic Erasing and Pancreatic Differentiation of Dermal Fibroblasts into Insulin-Producing Cells are Boosted by the Use of Low-Stiffness Substrate.

Georgia Pennarossa, Rosaria Santoro, Elena F M Manzoni, Maurizio Pesce, Fulvio Gandolfi, Tiziana A L Brevini

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Stem cell reviews and reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 35 citations in OpenAlex.

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  12. Mechanical regulation of histone modifications and cell plasticity.Current opinion in solid state & materials science · 2020
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  13. Adding a dimension to cell fate.Animal reproduction · 2020
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  17. Pluripotent Cell Models for Gonadal Research.International journal of molecular sciences · 2019
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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

6 authors at 2 institutions in 1 country.

Georgia PennarossaLaboratory of Biomedical Embryology, Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy.
Rosaria SantoroUnità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino-IRCCS, Milan, 20138, Italy.
Elena F M ManzoniLaboratory of Biomedical Embryology, Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy.
Maurizio PesceUnità di Ingegneria Tissutale Cardiovascolare, Centro Cardiologico Monzino-IRCCS, Milan, 20138, Italy.
Fulvio GandolfiLaboratory of Biomedical Embryology, Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy.
Tiziana A L BreviniLaboratory of Biomedical Embryology, Center for Stem Cell Research, Università degli Studi di Milano, Via Celoria 10, Milan, 20133, Italy. tiziana.brevini@unimi.it.
University of Milan · ITCentro Cardiologico Monzino · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Several studies have demonstrated the possibility to revert differentiation process, reactivating hypermethylated genes and facilitating cell transition to a different lineage. Beside the epigenetic mechanisms driving cell conversion processes, growing evidences highlight the importance of mechanical forces in supporting cell plasticity and boosting differentiation. Here, we describe epigenetic erasing and conversion of dermal fibroblasts into insulin-producing cells (EpiCC), and demonstrate that the use of a low-stiffness substrate positively influences these processes. Our results show a higher expression of pluripotency genes and a significant bigger decrease of DNA methylation levels in 5-azacytidine (5-aza-CR) treated cells plated on soft matrix, compared to those cultured on plastic dishes. Furthermore, the use of low-stiffness also induces a significant increased up-regulation of ten-eleven translocation 2 (Tet2) and histone acetyltransferase 1 (Hat1) genes, and more decreased histone deacetylase enzyme1 (Hdac1) transcription levels. The soft substrate also encourages morphological changes, actin cytoskeleton re-organization, and the activation of the Hippo signaling pathway, leading to yes-associated protein (YAP) phosphorylation and its cytoplasmic translocation. Altogether, this results in increased epigenetic conversion efficiency and in EpiCC acquisition of a mono-hormonal phenotype. Our findings indicate that mechano-transduction related responsed influence cell plasticity induced by 5-aza-CR and improve fibroblast differentiation toward the pancreatic lineage.

Indexed as

AnimalsAzacitidineBlotting, WesternCell DifferentiationCells, CulturedDNA MethylationEpigenesis, GeneticFibroblastsFlow CytometryHistocompatibilityInsulinMaleMiceMice, Inbred C57BLPancreasSignal TransductionAzacitidineInsulin5-AzacytidineCell plasticityEpigenetic conversionHippo signaling pathwayInsulin-producing cellsMatrix elasticity

Identifiers

PMID29285667
OpenAlexW2778351249

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.