Evidence map›Paper›PMID 35023014›Full record

ArticleProtein & cell2022

Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis.

Yuting Wang, Liping Liu, Yifan Song, Xiaojie Yu, Hongkui Deng

Open access · diamondAbstract read
In one paragraph

Article in Protein & cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  4. Review
  5. Chromatin accessibility regulates age-dependent nuclear mechanotransduction.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  18. Potential Targets Related to Skin Aging: Based on eQTL and GWAS Datasets.Clinical, cosmetic and investigational dermatology · 2025
    Article
  19. Spatial transcriptomics reveals Inhba/Smad2/E2f4 axis in Lrp2Frontiers in cell and developmental biology · 2025
    Article
  20. Article
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

5 authors at 1 institution in 1 country.

Yuting Wang *School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.ORCID 0000-0002-7253-5317
Liping Liu *School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.ORCID 0000-0003-3684-8591
Yifan Song *The MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.ORCID 0000-0002-0512-7153
Xiaojie YuThe MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.ORCID 0000-0003-4373-0321
Hongkui DengSchool of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. hongkui_deng@pku.edu.cn.ORCID 0000-0003-3045-4428
Peking University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulations, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (p16) expression in pre-senescent fibroblasts. Taken together, the results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.

Indexed as

Cellular SenescenceE2F4 Transcription FactorTEA Domain Transcription FactorsTranscription Factor AP-1AgingAnimalsFibroblastsMiceTranscriptomeE2f4 protein, mouseE2F4 Transcription FactorTead1 protein, mouseTEA Domain Transcription FactorsTranscription Factor AP-1multi-omicssenescencetranscription factor

Identifiers

PMID35023014
PMCPMC9233726
OpenAlexW4206631254

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.