Evidence map›Paper›PMID 33601339›Full record

ArticleAging2021

Insights into epithelial cell senescence from transcriptome and secretome analysis of human oral keratinocytes.

Rachael E Schwartz, Maxim N Shokhirev, Leonardo R Andrade, J Silvio Gutkind, Ramiro Iglesias-Bartolome, Gerald S Shadel

Open access · greenAbstract read
In one paragraph

Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 19 citations in OpenAlex.

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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 3 institutions in 1 country.

Rachael E SchwartzMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies and University of California - San Diego, La Jolla, CA 92037, USA.
Maxim N ShokhirevRazavi Newman Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Leonardo R AndradeWaitt Advanced Biophotonics Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
J Silvio GutkindDepartment of Pharmacology and Moores Cancer Center, University of California - San Diego, La Jolla, CA 92093, USA.
Ramiro Iglesias-BartolomeCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Gerald S ShadelMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies and University of California - San Diego, La Jolla, CA 92037, USA.
Salk Institute for Biological Studies · USUniversity of California, San Diego · USCenter for Cancer Research · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
Signaling pathways regulating stem cell fate decisionsZIABC011763 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI IGLESIAS-BARTOLOME, RAMIRO · 2017 to 2025
$7.5M
NCI NIH HHS P30 CA014195
6 · The paper itself

Abstract

Senescent cells produce chronic inflammation that contributes to the diseases and debilities of aging. How this process is orchestrated in epithelial cells, the origin of human carcinomas, is poorly understood. We used human normal oral keratinocytes (NOKs) to elucidate senescence programs in a prototype primary mucosal epithelial cell that senesces spontaneously. While NOKs exhibit several typical facets of senescence, they also display distinct characteristics. These include expression of p21WAF1/CIP1 at early passages, making this common marker of senescence unreliable in NOKs. Transcriptome analysis by RNA-seq revealed specific commonalities with and differences from cancer cells, explicating the tumor avoidance role of senescence. Repression of DNA repair genes that correlated with downregulation of E2F1 mRNA and protein was observed for two donors; a divergent result was seen for the third. Using proteomic profiling of soluble (non-vesicular) and extracellular vesicle (EV) associated secretions, we propose additions to the senescence associated secretory phenotype, including HSP60, which localizes to the surface of EVs. Finally, EVs from senescent NOKs activate interferon pathway signaling in THP-1 monocytes in a STING-dependent manner and associate with mitochondrial and nuclear DNA. Our results highlight senescence changes in epithelial cells and how they might contribute to chronic inflammation and age-related diseases.

Indexed as

Gene Expression ProfilingMouth MucosaCellular SenescenceEpithelial CellsExtracellular VesiclesHumansKeratinocytesSequence Analysis, RNASignal Transductioncarcinomacellular senescenceextracellular vesiclesinflammationkeratinocytes

Identifiers

PMID33601339
PMCPMC7950289
OpenAlexW3131101747

What OpenQuestion holds

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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.