Evidence map›Paper›PMID 34572080›Full record

ArticleCells2021

Uncovering the Metabolic and Stress Responses of Human Embryonic Stem Cells to

Luana Scaramuzzino, Valeria Lucchino, Stefania Scalise, Michela Lo Conte, Clara Zannino, Alessandro Sacco, Flavia Biamonte, Elvira Immacolata Parrotta, Francesco Saverio Costanzo, Giovanni Cuda

Open access · goldAbstract read
In one paragraph

Article in Cells, 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
1.5field-weighted citation impact, top 18% 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, 24 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

10 authors at 1 institution in 1 country.

Luana ScaramuzzinoResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.ORCID 0000-0003-3239-3745
Valeria LucchinoResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.
Stefania ScaliseResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.ORCID 0000-0001-6979-1486
Michela Lo ConteResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.
Clara ZanninoResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.
Alessandro SaccoResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.
Flavia BiamonteResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.ORCID 0000-0003-3248-3863
Elvira Immacolata ParrottaDepartment of Medical and Surgical Sciences, University Magna Graecia, 88100 Catanzaro, Italy.ORCID 0000-0001-8145-3623
Francesco Saverio CostanzoResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.
Giovanni CudaResearch Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, University Magna Graecia, 88100 Catanzaro, Italy.ORCID 0000-0001-6313-1866
Magna Graecia University · IT

Funding

Ministero dell'Istruzione, dell'Università e della Ricerca PRIN 2017CH4RNP_001 to GC
6 · The paper itself

Abstract

Embryonic stem cells (ESCs) are pluripotent cells with indefinite self-renewal ability and differentiation properties. To function properly and maintain genomic stability, ESCs need to be endowed with an efficient repair system as well as effective redox homeostasis. In this study, we investigated different aspects involved in ESCs' response to iron accumulation following stable knockdown of the ferritin heavy chain (FTH1) gene, which encodes for a major iron storage protein with ferroxidase activity. Experimental findings highlight unexpected and, to a certain extent, paradoxical results. If on one hand FTH1 silencing does not correlate with increased ROS production nor with changes in the redox status, strengthening the concept that hESCs are extremely resistant and, to a certain extent, even refractory to intracellular iron imbalance, on the other, the differentiation potential of hESCs seems to be affected and apoptosis is observed. Interestingly, we found that FTH1 silencing is accompanied by a significant activation of the nuclear factor (erythroid-derived-2)-like 2 (Nrf2) signaling pathway and pentose phosphate pathway (PPP), which crosstalk in driving hESCs antioxidant cascade events. These findings shed new light on how hESCs perform under oxidative stress, dissecting the molecular mechanisms through which Nrf2, in combination with PPP, counteracts oxidative injury triggered by FTH1 knockdown.

Indexed as

Oxidative StressAntioxidant Response ElementsApoptosisCell DifferentiationCells, CulturedFerritinsGene SilencingHuman Embryonic Stem CellsHumansNF-E2-Related Factor 2Oxidation-ReductionOxidoreductasesPentose Phosphate PathwaySignal TransductionFerritinsFTH1 protein, humanNFE2L2 protein, humanNF-E2-Related Factor 2OxidoreductasesFTH1human embryonic stem cells (hESCs)metabolic reroutingNrf2oxidative stressredox regulation

Identifiers

PMID34572080
PMCPMC8469604
OpenAlexW3200797015

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.