Protocol for siRNA-mediated TET1 knockdown during differentiation of human embryonic stem cells into definitive endoderm cells DOI Creative Commons
Zhongqi Liufu, Yujian Liu, Jiangping He

et al.

STAR Protocols, Journal Year: 2023, Volume and Issue: 4(3), P. 102455 - 102455

Published: July 18, 2023

TET1-mediated active DNA demethylation is required for endogenous retrovirus (ERV) enhancer activation during human ES differentiation into definitive endoderm (DE) cells. Here we present a protocol siRNA-mediated TET1 knockdown this process to decipher TET1's role in ERV and DE differentiation. We describe steps inducing then detail knocking down examining the effects of on LTR6B methylation, cell morphology, gene expression. For complete details use execution protocol, please refer Wu et al. (2022).

Language: Английский

Endogenous retroviruses in development and health DOI Open Access
Jichang Wang, Xinyi Lu, Weiqi Zhang

et al.

Trends in Microbiology, Journal Year: 2023, Volume and Issue: 32(4), P. 342 - 354

Published: Oct. 4, 2023

Language: Английский

Citations

32
Ribosomal profiling of human endogenous retroviruses in healthy tissues DOI Creative Commons
Nicholas Dopkins, B. K. Singh, Stephanie Michael

et al.

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 2, 2024

Abstract Human endogenous retroviruses (HERVs) are the germline embedded proviral fragments of ancient retroviral infections that make up roughly 8% human genome. Our understanding HERVs in physiology primarily surrounds their non-coding functions, while protein coding capacity remains virtually uncharacterized. Therefore, we applied bioinformatic pipeline “hervQuant” to high-resolution ribosomal profiling healthy tissues provide a comprehensive overview translationally active HERVs. We find account for 0.1–0.4% all translation distinct tissue-specific profiles. Collectively, our study further supports claims actively translated throughout sequences origin proteome.

Language: Английский

Citations

6
Species-Specific Transcription Factors Associated with Long Terminal Repeat Promoters of Endogenous Retroviruses: A Comprehensive Review DOI Creative Commons
Md. Jakir Hossain,

Perpetual Nyame,

Kazuaki Monde

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 280 - 280

Published: Feb. 26, 2024

Endogenous retroviruses (ERVs) became a part of the eukaryotic genome through endogenization millions years ago. Moreover, they have lost their innate capability virulence or replication. Nevertheless, in cells, actively engage various activities that may be advantageous disadvantageous to cells. The mechanisms by which transcription is triggered and implicated cellular processes are complex. Owing diversity expression factors (TFs) cells TF-binding motifs viruses, comprehensibility ERV initiation its impact on functions unclear. Currently, several known related initiation. TFs bind viral long-terminal repeat (LTR) critical initiators. This review discusses shown associate with stimulation across species such as humans, mice, pigs, monkeys, zebrafish, Drosophila, yeast. A comprehensive summary previously reported aid identifying similarities between animal endogenous viruses. an in-depth understanding will assist elucidating physiological roles cell development clarifying relationship retrovirus-associated diseases.

Language: Английский

Citations

4
TET activity safeguards pluripotency throughout embryonic dormancy DOI Creative Commons

Maximilian Stötzel,

Chieh-Yu Cheng,

Ibrahim A. IIik

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(10), P. 1625 - 1639

Published: May 23, 2024

Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos mammals are preservable weeks to months within uterus in a dormant state called diapause, which can be induced vitro mTOR inhibition. Cellular strategies that safeguard original cell identity silent genomic landscape dormancy not known. Here we show protection cis-regulatory elements from silencing key maintaining pluripotency state. We reveal TET-transcription factor axis, TET-mediated DNA demethylation recruitment methylation-sensitive transcription TFE3 drive transcriptionally inert chromatin adaptations during transition. Perturbation TET activity compromises survival mouse under dormancy, whereas its enhancement improves rates. Our results mechanism propagating cellular cells, with implications regeneration disease.

Language: Английский

Citations

3
ATRX guards against aberrant differentiation in mesenchymal progenitor cells DOI Creative Commons
Fang Yan, Douglas Barrows,

Yakshi Dabas

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(9), P. 4950 - 4968

Published: March 13, 2024

Abstract Alterations in the tumor suppressor ATRX are recurrently observed mesenchymal neoplasms. has multiple epigenetic functions including heterochromatin formation and maintenance regulation of transcription through modulation chromatin accessibility. Here, we show murine progenitor cells (MPCs) that Atrx deficiency aberrantly activated differentiation programs. This includes adipogenic pathways where loss induced expression factors enhanced response to stimuli. These changes linked near lineage genes together with increased accessibility gains active marks. We additionally depletion H3K9me3 at transposable elements, which derepressed they could serve as regulatory elements. Finally, demonstrated a malignancy, undifferentiated pleomorphic sarcoma, results similar disruption de-repression Together, our reveal role for maintaining states transcriptional repression progenitors preventing aberrant context.

Language: Английский

Citations

2
TET1 facilitates specification of early human lineages including germ cells DOI Creative Commons
Fei‐Man Hsu,

Qiu Ya Wu,

Emily B. Fabyanic

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(7), P. 107191 - 107191

Published: June 21, 2023

Ten Eleven Translocation 1 (TET1) is a regulator of localized DNA demethylation through the conversion 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). To examine in human primordial germ cell-like cells (hPGCLCs) induced from embryonic stem (hESCs), we performed bisulfite-assisted APOBEC coupled epigenetic sequencing (bACEseq) followed by integrated genomics analysis. Our data indicates that 5hmC enriches at hPGCLC-specific NANOG, SOX17 or TFAP2C binding sites on hPGCLC induction, and this accompanied demethylation. Using CRISPR-Cas9, show deleting catalytic domain TET1 reduces competency when starting with hESC cultured mouse fibroblasts, phenotype can be rescued after transitioning hESCs defined media recombinant substrate. Taken together, our study demonstrates importance facilitating competency, role culture conditions modulating effect.

Language: Английский

Citations

2
Heterochromatin protein ERH represses alternative cell fates during early mammalian differentiation DOI Open Access
Andrew Katznelson,

Blake Hernandez,

Holly Fahning

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 6, 2024

Abstract Enhancer of Rudimentary Homolog (ERH) is an evolutionarily conserved protein originally characterized in fission yeast 1 and recently shown to maintain H3K9me3 human fibroblasts 2 . Here, we find that ERH depletion reverts the landscape embryonic stem cell (ESC) state enables activation naïve pluripotency genes transposable elements during induced pluripotent (iPSC) reprogramming. We similarly represses totipotent alternative lineage programs mouse preimplantation development required for proper segregation inner mass trophectoderm lineages. During ESC differentiation into germ layer lineages, silences genes, elements, somatic genes. As yeast, mammalian interacts with RNA-binding proteins engage repress its chromatin targets. Our findings reveal a fundamental role fate specification via initiation maintenance early developmental gene repression.

Language: Английский

Citations

0
Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming DOI Creative Commons

Yuling Peng,

Jieying Zhu,

Qi Zhang

et al.

Cell Regeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 13, 2024

Endogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver evolutionary changes, offering insight into mechanisms. In our study, we explored functionality ERVs by examining single-cell transcriptomic profiles from human stem cells urine cells. This led discovery a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic reprogramming efficacy was enhanced when overexpressed cell-reprogramming system. Induced pluripotent (iPSCs) generated with overexpression recapitulated traits those produced traditional approaches, resulting iPSCs demonstrated capability differentiate all three germ layers vitro. Our research elucidated role reprogramming.

Language: Английский

Citations

0
Protocol for siRNA-mediated TET1 knockdown during differentiation of human embryonic stem cells into definitive endoderm cells DOI Creative Commons
Zhongqi Liufu, Yujian Liu, Jiangping He

et al.

STAR Protocols, Journal Year: 2023, Volume and Issue: 4(3), P. 102455 - 102455

Published: July 18, 2023

TET1-mediated active DNA demethylation is required for endogenous retrovirus (ERV) enhancer activation during human ES differentiation into definitive endoderm (DE) cells. Here we present a protocol siRNA-mediated TET1 knockdown this process to decipher TET1's role in ERV and DE differentiation. We describe steps inducing then detail knocking down examining the effects of on LTR6B methylation, cell morphology, gene expression. For complete details use execution protocol, please refer Wu et al. (2022).

Language: Английский

Citations

0