Circular RNA circPLOD2 regulates pericyte function by targeting the transcription factor KLF4 Article Swipe
Simone F. Glaser
,
Andre Brezski
,
Nina Baumgarten
,
Marius Klangwart
,
Andreas W. Heumüller
,
Ranjan Kumar Maji
,
Matthias S. Leisegang
,
Stefan Guenther
,
Christoph M. Zehendner
,
David John
,
Marcel H. Schulz
,
Kathi Zarnack
,
Stefanie Dimmeler
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.12.04.519017
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.12.04.519017
Circular RNAs (circRNAs) are generated by back-splicing and control cellular signaling and phenotypes. Pericytes stabilize the capillary structure and play an important role in the formation and maintenance of new blood vessels. Here, we characterized hypoxia-regulated circRNAs in human pericytes and showed that circPLOD2 is induced by hypoxia and regulates pericyte function. Silencing of circPLOD2 increased pericyte proliferation, endothelial-pericyte interaction and tube formation. Transcriptional profiling of circPLOD2-depleted cells and epigenomic analyses revealed widespread changes in gene expression and identified the circPLOD2-dependent regulation of the transcription factor KLF4 as a key effector of these changes. Importantly, overexpression of KLF4 was sufficient to reverse the effects on pericyte proliferation and endothelial-pericyte interactions observed after circPLOD2 depletion. Together, these data revealed a novel function of circPLOD2 in the control of pericyte proliferation and capillary formation and showed that circPLOD2-mediated regulation of KLF4 significantly contributes to the transcriptional response to hypoxia. Highlights circPLOD2 is upregulated in hypoxia in human vascular pericytes Selective depletion of circPLOD2, but not linear PLOD2 mRNA, changes pericyte migration and endothelial-pericyte interaction circPLOD2 depletion triggers widespread changes in gene expression that are mirrored in the transcriptional hypoxia response Epigenomic analyses pinpoint the transcription factor KLF4 as a central player in circPLOD2-mediated expression changes KLF4 overexpression is sufficient to rescue the changes in pericyte function caused by circPLOD2 depletion
Related Topics
Concepts
Pericyte
KLF4
Cell biology
Biology
Transcription factor
Gene silencing
Transcriptional regulation
Downregulation and upregulation
Endothelial stem cell
Gene
Genetics
In vitro
SOX2
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.12.04.519017
- https://www.biorxiv.org/content/biorxiv/early/2022/12/04/2022.12.04.519017.full.pdf
- OA Status
- green
- Cited By
- 2
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4310670610
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4310670610Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2022.12.04.519017Digital Object Identifier
- Title
-
Circular RNA circPLOD2 regulates pericyte function by targeting the transcription factor KLF4Work title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-12-04Full publication date if available
- Authors
-
Simone F. Glaser, Andre Brezski, Nina Baumgarten, Marius Klangwart, Andreas W. Heumüller, Ranjan Kumar Maji, Matthias S. Leisegang, Stefan Guenther, Christoph M. Zehendner, David John, Marcel H. Schulz, Kathi Zarnack, Stefanie DimmelerList of authors in order
- Landing page
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https://doi.org/10.1101/2022.12.04.519017Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2022/12/04/2022.12.04.519017.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2022/12/04/2022.12.04.519017.full.pdfDirect OA link when available
- Concepts
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Pericyte, KLF4, Cell biology, Biology, Transcription factor, Gene silencing, Transcriptional regulation, Downregulation and upregulation, Endothelial stem cell, Gene, Genetics, In vitro, SOX2Top concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2023: 2Per-year citation counts (last 5 years)
- References (count)
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46Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.stabilize | 15 |
| abstract_inverted_index.structure | 18 |
| abstract_inverted_index.(circRNAs) | 3 |
| abstract_inverted_index.Epigenomic | 189 |
| abstract_inverted_index.Highlights | 148 |
| abstract_inverted_index.circPLOD2, | 161 |
| abstract_inverted_index.depletion. | 114 |
| abstract_inverted_index.epigenomic | 70 |
| abstract_inverted_index.expression | 77, 180, 202 |
| abstract_inverted_index.formation. | 63 |
| abstract_inverted_index.identified | 79 |
| abstract_inverted_index.regulation | 82, 137 |
| abstract_inverted_index.sufficient | 100, 207 |
| abstract_inverted_index.widespread | 73, 176 |
| abstract_inverted_index.contributes | 141 |
| abstract_inverted_index.interaction | 60, 172 |
| abstract_inverted_index.maintenance | 28 |
| abstract_inverted_index.phenotypes. | 13 |
| abstract_inverted_index.upregulated | 151 |
| abstract_inverted_index.Importantly, | 95 |
| abstract_inverted_index.interactions | 110 |
| abstract_inverted_index.back-splicing | 7 |
| abstract_inverted_index.characterized | 35 |
| abstract_inverted_index.proliferation | 107, 129 |
| abstract_inverted_index.significantly | 140 |
| abstract_inverted_index.transcription | 85, 193 |
| abstract_inverted_index.overexpression | 96, 205 |
| abstract_inverted_index.proliferation, | 58 |
| abstract_inverted_index.Transcriptional | 64 |
| abstract_inverted_index.transcriptional | 144, 186 |
| abstract_inverted_index.hypoxia-regulated | 36 |
| abstract_inverted_index.circPLOD2-depleted | 67 |
| abstract_inverted_index.circPLOD2-mediated | 136, 201 |
| abstract_inverted_index.circPLOD2-dependent | 81 |
| abstract_inverted_index.endothelial-pericyte | 59, 109, 171 |
| cited_by_percentile_year.max | 96 |
| cited_by_percentile_year.min | 94 |
| corresponding_author_ids | https://openalex.org/A5025706940 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 13 |
| corresponding_institution_ids | https://openalex.org/I114090438, https://openalex.org/I4210127591 |
| citation_normalized_percentile.value | 0.51653097 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |