A multi-omics integrative analysis based on CRISPR screens re-defines the pluripotency regulatory network in ESCs
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Abstract
A comprehensive and precise definition of the pluripotency gene regulatory network (PGRN) is crucial for clarifying the regulatory mechanisms in embryonic stem cells (ESCs). Here, after a CRISPR/Cas9-based functional genomics screen and integrative analysis with other functional genomes, transcriptomes, proteomes and epigenome data, an expanded pluripotency-associated gene set is obtained, and a new PGRN with nine sub-classes is constructed. By integrating the DNA binding, epigenetic modification, chromatin conformation, and RNA expression profiles, the PGRN is resolved to six functionally independent transcriptional modules (CORE, MYC, PAF, PRC, PCGF and TBX). Spatiotemporal transcriptomics reveal activated CORE/MYC/PAF module activity and repressed PRC/PCGF/TBX module activity in both mouse ESCs (mESCs) and pluripotent cells of early embryos. Moreover, this module activity pattern is found to be shared by human ESCs (hESCs) and cancers. Thus, our results provide novel insights into elucidating the molecular basis of ESC pluripotency.
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Combining sequence analyses with multi-omics data markedly improves off-target predictions across various cell lines.
“A study demonstrated that combining sequence analyses with multi-omics data markedly improves off-target predictions across various cell lines.”
From Hybrid Neural Networks for Off-Target Prediction in Gene Editing: Integrating Sequence and Biophysical Features (2025) · cites this paper as [9]
The Introduction (page not available) discusses multi-omics analysis of pluripotency networks and mentions low off-target effects, but not off-target prediction. The Discussion (page not available) describes predicting transcription-factor target genes instead. Searches for off-target prediction and sequence analysis across cell lines found no passage addressing the claim. (LLM, conf=0.76)
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Sorted by citations
Verma, P. (2025) · International Journal of High School Research · doi:10.36838/v7i2.113 · Cited by 1 · see citing works
- Authors
- Ruan, Y., Wang, J., Yu, M., Wang, F., Wang, J., Xu, Y., Liu, L., Cheng, Y., Yang, R., Zhang, C., Yang, Y., Wang, J., Wu, W., Huang, Y., Tian, Y., Chen, G., Zhang, J., & Jian, R.
- Affiliations
- Army Medical University (CN)
- Corresponding author
- Zhang, Chen
- Chen, Guangxing
- Zhang, Junlei
- Jian, Rui
- ORCID
- Venue
- Communications Biology
- Published
- 2023-04-14
- Volume
- 6
- Issue
- 1
- Pages
- 410-410
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC10104827
- OpenAlex
- W4365510946
- Cited by
- 11
- References
- 6
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31571442)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- embryonic stem cell pluripotency, multi-omics integration, transcriptional modules, chromatin conformation, epigenetic modifications, spatiotemporal transcriptomics
- MeSH terms
- Mouse Embryonic Stem Cells, Multiomics, Animals, Chromatin, Humans, Pluripotent Stem Cells, Mice, Embryonic Stem Cells
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