Movements of Ancient Human Endogenous Retroviruses Detected in SOX2-Expressing Cells

Monde, Kazuaki; Satou, Yorifumi; Goto, Mizuki; Uchiyama, Yoshikazu; Ito, Jumpei; Kaitsuka, Taku; Terasawa, Hiromi; Monde, Nami; Yamaga, Shinya; Matsusako, Tomoya; Wei, Fan Yan; Inoue, Ituro; Tomizawa, Kazuhito; Ono, Akira; Era, Takumi; Sawa, Tomohiro; Maeda, Yosuke

doi:10.1128/jvi.00356-22

Cited by 9 publications

(13 citation statements)

References 66 publications

(85 reference statements)

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“…S1D ). Recently, it was reported that SOX2, an important marker of initialization and pluripotency in undifferentiated cells, induces genome expression in human endogenous retroviruses (HERVs) [ 26 ]. We investigated the initialization state of iPSCs by analysing expression of HERVs.…”

Section: Resultsmentioning

confidence: 99%

“…The primers for human OCT3/4, human NANOG, human SOX2, human β-actin, human integrin α1, human integrin α5, human integrin α6, human integrin αV, human integrin β1, human integrin β3, human integrin β4 and human CDH1 and human GAPDH were designed using the Primer 3 Plus application ( http://www.bioinformatics.nl/cgi-bin/primer3plus/primer3plus.cgi ). The primer sequence for HERV-K Gag CA was selected from the sequence described in a previous paper [ 26 ]. Other primers were purchased from Takara Bio Inc. (Shiga, Japan).…”

Section: Methodsmentioning

confidence: 99%

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Semi-3D cultures using Laminin 221 as a coating material for human induced pluripotent stem cells

Nakashima

Yoshida

Tsukahara

2022

Regenerative Biomaterials

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It was previously believed that human induced pluripotent stem cells (hiPSCs) did not show adhesion to the coating material laminin 221, which is known to have specific affinity for cardiomyocytes. In this study, we report that human mononuclear cell-derived hiPSCs, established with Sendai virus vector, form peninsular-like colonies rather than embryonic stem cell-like colonies; these peninsular-like colonies can be passaged more than 10 times after establishment. Additionally, initialization-deficient cells with residual Sendai virus vector adhered to the coating material Laminin 511 but not to Laminin 221. Therefore, the expression of undifferentiated markers tended to be higher in hiPSCs established on Laminin 221 than on Laminin 511. On Laminin 221, hiPSCs15M66 showed a semi-floating colony morphology. The expression of various markers of cell polarity was significantly lower in hiPSCs cultured on Laminin 221 than in hiPSCs cultured on Laminin 511. Furthermore, 201B7 and 15M66 hiPSCs showed three-dimensional cardiomyocyte differentiation on Laminin 221. Thus, the coating material Laminin 221 provides semi-floating culture conditions for the establishment, culture, and induced differentiation of hiPSCs.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Semi-3D cultures using Laminin 221 as a coating material for human induced pluripotent stem cells

Nakashima

Yoshida

Tsukahara

2022

Regenerative Biomaterials

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“…Transcription factor binding sites (TFBSs) have been observed in association with HERVs and LTRs, regulating the transcriptional activity of these exogenous elements ( Monde et al, 2022 ; Liu et al, 2022 ). In order to determine the transcription factors (TFs) associated exclusively with ERVs, we excluded all the TFBSs shared by orthologs and paralogs annotated in structural equivalent sections.…”

Section: Resultsmentioning

confidence: 99%

“…Another interesting question related to the transcription factor analysis is whether the transcription factor binding sites can activate or deactivate ERVs ( Grow et al, 2015 ; Monde et al, 2022 ). A frequent target of ERV silencing is the so-called primer binding site (PBS), although there are other described mechanisms associated with this process.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary analysis of endogenous intronic retroviruses in primates reveals an enrichment in transcription binding sites associated with key regulatory processes

Calero-Layana

López-Cruz

Ocaña

et al. 2022

PeerJ

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Background Endogenous retroviruses (ERVs) are the result of the integration of retroviruses into host DNA following germline infection. Endogenous retroviruses are made up of three main genes: gag, pol, and env, each of which encodes viral proteins that can be conserved or not. ERVs have been observed in a wide range of vertebrate genomes and their functions are associated with viral silencing and gene regulation. Results In this work, we studied the evolutionary history of endogenous retroviruses associated with five human genes (INPP5B, DET1, PSMA1, USH2A, and MACROD2), which are located within intron sections. To verify the retroviral origin of the candidates, several approaches were used to detect and locate ERV elements. Both orthologous and paralogous genes were identified by Ensembl and then analyzed for ERV presence using RetroTector. A phylogenetic tree was reconstructed to identify the minimum time point of ERV acquisition. From that search, we detected ERVs throughout the primate lineage and in some other groups. Also, we identified the minimum origin of the ERVs from the parvorder Catarrhini to the Homininae subfamily. Conclusions With the data collected, and by observing the transcription factors annotated inside ERVs, we propose that these elements play a relevant role in gene expression regulation and they probably possess important features for tumorigenesis control.

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“…HERVs are flanked by two long terminal repeats (LTRs) that contain the regulation part of the retrovirus. However, most HERVs are present as solo LTRs [ 46 ]. The most studied HERV group is the W group, which is specifically mobilized by the LINE-1 machinery [ 43 ].…”

Section: Endogenous Viral Elementsmentioning

confidence: 99%

Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and Challenges in Analysis Methods

Štangar

Kovač

Šket

et al. 2023

IJMS

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Type 1 diabetes (T1D) is one of the most common chronic diseases of the endocrine system, associated with several life-threatening comorbidities. While the etiopathogenesis of T1D remains elusive, a combination of genetic susceptibility and environmental factors, such as microbial infections, are thought to be involved in the development of the disease. The prime model for studying the genetic component of T1D predisposition encompasses polymorphisms within the HLA (human leukocyte antigen) region responsible for the specificity of antigen presentation to lymphocytes. Apart from polymorphisms, genomic reorganization caused by repeat elements and endogenous viral elements (EVEs) might be involved in T1D predisposition. Such elements are human endogenous retroviruses (HERVs) and non-long terminal repeat (non-LTR) retrotransposons, including long and short interspersed nuclear elements (LINEs and SINEs). In line with their parasitic origin and selfish behaviour, retrotransposon-imposed gene regulation is a major source of genetic variation and instability in the human genome, and may represent the missing link between genetic susceptibility and environmental factors long thought to contribute to T1D onset. Autoreactive immune cell subtypes with differentially expressed retrotransposons can be identified with single-cell transcriptomics, and personalized assembled genomes can be constructed, which can then serve as a reference for predicting retrotransposon integration/restriction sites. Here we review what is known to date about retrotransposons, we discuss the involvement of viruses and retrotransposons in T1D predisposition, and finally we consider challenges in retrotransposons analysis methods.

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Movements of Ancient Human Endogenous Retroviruses Detected in SOX2-Expressing Cells

Abstract: Human endogenous retroviruses (HERVs) account for approximately 8% of the human genome; however, the physiological role of HERV-K remains unknown. This study found that HERV-K LTR5Hs and LTR5B were transactivated by SOX2, which is essential for maintaining and reestablishing pluripotency.

Cited by 9 publications

References 66 publications

Semi-3D cultures using Laminin 221 as a coating material for human induced pluripotent stem cells

Semi-3D cultures using Laminin 221 as a coating material for human induced pluripotent stem cells

Evolutionary analysis of endogenous intronic retroviruses in primates reveals an enrichment in transcription binding sites associated with key regulatory processes

Contribution of Retrotransposons to the Pathogenesis of Type 1 Diabetes and Challenges in Analysis Methods

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