Isolation and cultivation of naive-like human pluripotent stem cells based on HERVH expression

Wang, Jichang; Singh, Manvendra; Sun, Chuanbo; Besser, Daniel; Prigione, Alessandro; Ivics, Zoltán; Hurst, Laurence D.; Izsvák, Zsuzsanna

doi:10.1038/nprot.2016.016

Cited by 34 publications

(24 citation statements)

References 63 publications

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“…RNA-seq data in human embryonic and pluripotent stem cells revealed similar trends, where the HERVH subfamily is highly expressed and marked with the active promoter and enhancer chromatin marks (Wang et al 2016). Furthermore, a recent single-cell RNA-seq study also revealed the higher expression of ERVs at various stages of preimplantation embryogenesis in human and showed their ability to distinguish all cell-specific stages using TE transcription alone (Göke et al 2015).…”

Section: Introductionmentioning

confidence: 85%

Atlas of transcriptionally active transposable elements in human adult tissues

Bogu

Reverter

Martí‐Renom

et al. 2019

Preprint

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Approximately half of the human genome consists of mobile repetitive DNA sequences known as transposable elements (TEs). They are usually silenced by epigenetic mechanisms, but a few are known to escape silencing at embryonic stages, affecting early human development by regulating nearby protein-coding genes. To investigate transcriptional activity in human adult tissues we systematically investigate the expression landscape of about 4.2 million non-coding TEs in 8,051 RNA-Seq datasets from up to 49 adult tissues and 540 individuals. We show that approximately 79,558 individual TEs (2%).belonging to 856 subfamilies escape epigenetic silencing in adult tissues and become transcriptionally active, often in a very tissue-specific manner. Supporting a role for TEs in the regulation of expression of nearby genes, we found the expression of TEs often correlated with the expression of nearby genes, and significantly stronger when the TEs include eQTLs for the genes. We identified thousands of tissue-elevated, sex-associated TEs in the breast, ethnicity-associated in the skin and age-associated in the tibial artery, where we found a potential implication of two TE subfamilies in atherosclerosis. Our results suggest a functional role of TEs in the regulation of gene expression, support their implication in human phenotypes, and also serve as a comprehensive resource of transcriptionally active TEs in human adult tissues.

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Section: Introductionmentioning

confidence: 85%

Atlas of transcriptionally active transposable elements in human adult tissues

Bogu

Reverter

Martí‐Renom

et al. 2019

Preprint

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“…When isolated using cell sorting, HERVH‐GFP ‐high cells adopt a naïve‐like morphology compared to HERVH‐GFP ‐low/negative cells. Nonetheless, repeated re‐sorting is required to maintain a homogeneous population of naïve‐like hPSCs . The cell phenotype is also unclear given that endogenous HERVH transcription is associated with primed, and not with naïve, hPSCs …”

Section: Developing Methods To Identify and Isolate Naïve Hpscsmentioning

confidence: 99%

Identifying Human Naïve Pluripotent Stem Cells − Evaluating State‐Specific Reporter Lines and Cell‐Surface Markers

Collier

Rugg‐Gunn

2018

BioEssays

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Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re-evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed 'naïve' human pluripotent stem cells to distinguish them from the conventional 'primed' cells. Here, several transcriptional and epigenetic hallmarks of human pluripotent states in the recently described cell lines are reviewed and evaluated. Methods to derive and identify human naïve pluripotent stem cells are also discussed, with a focus on the uses and future developments of state-specific reporter cell lines and cell-surface proteins. Finally, opportunities and uncertainties in naïve stem cell biology are highlighted, and the current limitations of human naïve pluripotent stem cells considered, particularly in the context of differentiation.

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“…We also used 25 individual HERVs that represent each family for the enrichment analysis (Table 1). Most of the HERVs were found to be expressed HERV elements in previous reports [51–56]. HERVs and disease conditions were considered as associated events when Fisher’s exact p-value was <0.001 and the odds ratio was >1.…”

Section: Methodsmentioning

confidence: 99%

EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes

et al. 2017

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Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which contain the regulation part of the retrovirus. Remaining HERVs constitute 7% to 8% of the present day human genome, and most have been identified as solo LTRs. The HERV sequences have been associated with several molecular functions as well as certain diseases in human, but their roles in human diseases are yet to be established. We designed EnHERV to make accessible the identified endogenous retrovirus repetitive sequences from Repbase Update (a database of eukaryotic repetitive elements) that are present in the human genome. Defragmentation process was done to improve the RepeatMasker annotation output. The defragmented elements were used as core database in EnHERV. EnHERV is available at http://sysbio.chula.ac.th/enherv and can be searched using either gene lists of user interest or HERV characteristics. Besides the search function, EnHERV also provides an enrichment analysis function that allows users to perform enrichment analysis between selected HERV characteristics and user-input gene lists, especially genes with the expression profile of a certain disease. EnHERV will facilitate exploratory studies of specific HERV characteristics that control gene expression patterns related to various disease conditions. Here we analyzed 25 selected HERV groups/names from all four HERV superfamilies, using the sense and anti-sense directions of the HERV and gene expression profiles from 49 specific tissue and disease conditions. We found that intragenic HERVs were associated with down-regulated genes in most cancer conditions and in psoriatic skin tissues and associated with up-regulated genes in immune cells particularly from systemic lupus erythematosus (SLE) patients. EnHERV allowed the analysis of how different types of LTRs were differentially associated with specific gene expression profiles in particular disease conditions for further studies into their mechanisms and functions.

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Isolation and cultivation of naive-like human pluripotent stem cells based on HERVH expression

Cited by 34 publications

References 63 publications

Atlas of transcriptionally active transposable elements in human adult tissues

Atlas of transcriptionally active transposable elements in human adult tissues

Identifying Human Naïve Pluripotent Stem Cells − Evaluating State‐Specific Reporter Lines and Cell‐Surface Markers

EnHERV: Enrichment analysis of specific human endogenous retrovirus patterns and their neighboring genes

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