Academic Journal
Transcriptomic meta-analysis reveals ERRα-mediated oxidative phosphorylation is downregulated in Fuchs’ endothelial corneal dystrophy
| العنوان: | Transcriptomic meta-analysis reveals ERRα-mediated oxidative phosphorylation is downregulated in Fuchs’ endothelial corneal dystrophy |
|---|---|
| المؤلفون: | Zhang, Xunzhi, Kumar, Ashwani, Sathe, Adwait A., Mootha, V. Vinod, Xing, Chao |
| المساهمون: | Roy, Sanhita, National Eye Institute, Harrington Discovery Institute, University Hospitals, Research to Prevent Blindness |
| المصدر: | PLOS ONE ; volume 18, issue 12, page e0295542 ; ISSN 1932-6203 |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2023 |
| المجموعة: | PLOS Publications (via CrossRef) |
| الوصف: | Background Late-onset Fuchs’ endothelial corneal dystrophy (FECD) is a degenerative disease of cornea and the leading indication for corneal transplantation. Genetically, FECD patients can be categorized as with (RE+) or without (RE-) the CTG trinucleotide repeat expansion in the transcription factor 4 gene. The molecular mechanisms underlying FECD remain unclear, though there are plausible pathogenic models proposed for RE+ FECD. Method In this study, we performed a meta-analysis on RNA sequencing datasets of FECD corneal endothelium including 3 RE+ datasets and 2 RE- datasets, aiming to compare the transcriptomic profiles of RE+ and RE- FECD. Gene differential expression analysis, co-expression networks analysis, and pathway analysis were conducted. Results There was a striking similarity between RE+ and RE- transcriptomes. There were 1,184 genes significantly upregulated and 1,018 genes significantly downregulated in both RE+ and RE- cases. Pathway analysis identified multiple biological processes significantly enriched in both—mitochondrial functions, energy-related processes, ER-nucleus signaling pathway, demethylation, and RNA splicing were negatively enriched, whereas small GTPase mediated signaling, actin-filament processes, extracellular matrix organization, stem cell differentiation, and neutrophil mediated immunity were positively enriched. The translational initiation process was downregulated in the RE+ transcriptomes. Gene co-expression analysis identified modules with relatively distinct biological processes enriched including downregulation of mitochondrial respiratory chain complex assembly. The majority of oxidative phosphorylation (OXPHOS) subunit genes, as well as their upstream regulator gene estrogen-related receptor alpha ( ESRRA ), encoding ERRα, were downregulated in both RE+ and RE- cases, and the expression level of ESRRA was correlated with that of OXPHOS subunit genes. Conclusion Meta-analysis increased the power of detecting differentially expressed genes. Integrating differential ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1371/journal.pone.0295542 |
| الاتاحة: | http://dx.doi.org/10.1371/journal.pone.0295542 https://dx.plos.org/10.1371/journal.pone.0295542 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.B9B742AF |
| قاعدة البيانات: | BASE |
| ResultId |
1 |
|---|---|
| Header |
edsbas BASE edsbas.B9B742AF 961 3 Academic Journal academicJournal 960.976379394531 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsbas&AN=edsbas.B9B742AF&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
Array ( [0] => Array ( [Url] => http://dx.doi.org/10.1371/journal.pone.0295542# [Name] => EDS - BASE [Category] => fullText [Text] => View record in BASE [MouseOverText] => View record in BASE ) ) |
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Transcriptomic meta-analysis reveals ERRα-mediated oxidative phosphorylation is downregulated in Fuchs’ endothelial corneal dystrophy
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Zhang%2C+Xunzhi%22">Zhang, Xunzhi</searchLink><br /><searchLink fieldCode="AR" term="%22Kumar%2C+Ashwani%22">Kumar, Ashwani</searchLink><br /><searchLink fieldCode="AR" term="%22Sathe%2C+Adwait+A%2E%22">Sathe, Adwait A.</searchLink><br /><searchLink fieldCode="AR" term="%22Mootha%2C+V%2E+Vinod%22">Mootha, V. Vinod</searchLink><br /><searchLink fieldCode="AR" term="%22Xing%2C+Chao%22">Xing, Chao</searchLink> ) Array ( [Name] => Author [Label] => Contributors [Group] => Au [Data] => Roy, Sanhita<br />National Eye Institute<br />Harrington Discovery Institute, University Hospitals<br />Research to Prevent Blindness ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => PLOS ONE ; volume 18, issue 12, page e0295542 ; ISSN 1932-6203 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Public Library of Science (PLoS) ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2023 ) Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => PLOS Publications (via CrossRef) ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Background Late-onset Fuchs’ endothelial corneal dystrophy (FECD) is a degenerative disease of cornea and the leading indication for corneal transplantation. Genetically, FECD patients can be categorized as with (RE+) or without (RE-) the CTG trinucleotide repeat expansion in the transcription factor 4 gene. The molecular mechanisms underlying FECD remain unclear, though there are plausible pathogenic models proposed for RE+ FECD. Method In this study, we performed a meta-analysis on RNA sequencing datasets of FECD corneal endothelium including 3 RE+ datasets and 2 RE- datasets, aiming to compare the transcriptomic profiles of RE+ and RE- FECD. Gene differential expression analysis, co-expression networks analysis, and pathway analysis were conducted. Results There was a striking similarity between RE+ and RE- transcriptomes. There were 1,184 genes significantly upregulated and 1,018 genes significantly downregulated in both RE+ and RE- cases. Pathway analysis identified multiple biological processes significantly enriched in both—mitochondrial functions, energy-related processes, ER-nucleus signaling pathway, demethylation, and RNA splicing were negatively enriched, whereas small GTPase mediated signaling, actin-filament processes, extracellular matrix organization, stem cell differentiation, and neutrophil mediated immunity were positively enriched. The translational initiation process was downregulated in the RE+ transcriptomes. Gene co-expression analysis identified modules with relatively distinct biological processes enriched including downregulation of mitochondrial respiratory chain complex assembly. The majority of oxidative phosphorylation (OXPHOS) subunit genes, as well as their upstream regulator gene estrogen-related receptor alpha ( ESRRA ), encoding ERRα, were downregulated in both RE+ and RE- cases, and the expression level of ESRRA was correlated with that of OXPHOS subunit genes. Conclusion Meta-analysis increased the power of detecting differentially expressed genes. Integrating differential ... ) Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article in journal/newspaper ) Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English ) Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.1371/journal.pone.0295542 ) Array ( [Name] => URL [Label] => Availability [Group] => URL [Data] => http://dx.doi.org/10.1371/journal.pone.0295542<br />https://dx.plos.org/10.1371/journal.pone.0295542 ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => http://creativecommons.org/licenses/by/4.0/ ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsbas.B9B742AF ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Identifiers] => Array
(
[0] => Array
(
[Type] => doi
[Value] => 10.1371/journal.pone.0295542
)
)
[Languages] => Array
(
[0] => Array
(
[Text] => English
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Transcriptomic meta-analysis reveals ERRα-mediated oxidative phosphorylation is downregulated in Fuchs’ endothelial corneal dystrophy
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Zhang, Xunzhi
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Kumar, Ashwani
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Sathe, Adwait A.
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Mootha, V. Vinod
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xing, Chao
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Roy, Sanhita
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => National Eye Institute
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Harrington Discovery Institute, University Hospitals
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Research to Prevent Blindness
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 01
[M] => 01
[Type] => published
[Y] => 2023
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-locals
[Value] => edsbas
)
[1] => Array
(
[Type] => issn-locals
[Value] => edsbas.oa
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => PLOS ONE ; volume 18, issue 12, page e0295542 ; ISSN 1932-6203
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |