Evidence map›Paper›PMID 36672222›Full record

ArticleCells2023

Genome-Wide Methylation Changes Associated with Replicative Senescence and Differentiation in Endothelial and Bone Marrow Mesenchymal Stromal Cells.

Angelica Giuliani, Maria Giulia Bacalini, Deborah Ramini, Emanuela Mensà, Chiara Giordani, Luciano Xumerle, Paolo Garagnani, Fabiola Olivieri, Antonio Domenico Procopio, Maria Rita Rippo and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. mStem cell research & therapy · 2026
    Article
  2. 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

11 authors at 5 institutions in 2 countries.

Angelica GiulianiDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.ORCID 0000-0002-8477-8519
Maria Giulia BacaliniIRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
Deborah RaminiClinic of Laboratory and Precision Medicine, IRCCS INRCA, 60121 Ancona, Italy.ORCID 0000-0001-8925-8195
Emanuela MensàDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.
Chiara GiordaniDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.ORCID 0000-0003-1733-654X
Luciano XumerlePersonal Genomic S.R.L, 37134 Verona, Italy.
Paolo GaragnaniDepartment of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.
Fabiola OlivieriDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.
Antonio Domenico ProcopioDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.
Maria Rita RippoDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.ORCID 0000-0003-3024-3495
Jacopo SabbatinelliDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, 60126 Ancona, Italy.ORCID 0000-0001-9947-6778
Marche Polytechnic University · ITCenter for Genomic Science · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITIstituto delle Scienze Neurologiche di Bologna · ITKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bone marrow mesenchymal stromal cells (BMSCs) are multipotent cells able to self-renew and differentiate, depending on the microenvironment, into adipocytes and osteoblasts. These cells have a limited number of replications and enter replicative senescence during in vitro expansion. The role of DNA methylation (DNAm) assumes importance in cell function and commitment; however, its exact contribution to BMSC differentiation and replicative senescence is still unclear. We performed a genome-wide DNAm analysis on BMSCs cultured in vitro at early passages and induced to differentiate into adipocytes and osteoblasts, and on replicative senescent BMSCs and HUVECs, to identify DNAm patterns of senescence and differentiation. We also compared BMSCs and HUVECs in replicative senescence and found that, in both cellular systems, genome-wide hypomethylation was accompanied by a higher-than-expected overlap of differentially methylated positions (DMPs) and concordance in terms of direction of the change. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on lineage-independent senescence-associated DMPs revealed 16 common pathways, including Insulin resistance, Molecule adhesion, and Wnt/β-catenin signaling. In both adipogenesis and osteogenesis, we observed a general demethylation of CpG sites compared with undifferentiated BMSCs with a higher number of DMPs in osteogenesis. KEGG analysis resulted in 30 pathways enriched in osteoblasts and only 2 in adipocytes when compared to undifferentiated cells. When comparing differentiated BMSCs with senescent ones, osteogenesis exhibited a greater overlap with senescence in terms of number of DMPs and direction of methylation change compared to adipogenesis. In conclusion, this study may be useful for future research on general mechanisms that occur in replicative senescence and furthermore to identify trajectories of BMSC differentiation and common aspects of differentiated and senescent cells.

Indexed as

Bone MarrowMesenchymal Stem CellsCell DifferentiationCellular SenescenceDNA Methylationadipocytesbone-marrow mesenchymal stromal cellscellular senescenceDNA methylationendothelial cellsosteoblasts

Identifiers

PMID36672222
PMCPMC9857206
OpenAlexW4315796021

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.