ArticleGenome biology2024
Single-cell 3D genome structure reveals distinct human pluripotent states.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Structure Variations and 3D Genome Disruption: Implications in Safety of hPSC-Based Cell Therapy.International journal of molecular sciences · 2026Review
- NELFA supports naïve pluripotency and drives 8C-like state in human embryonic stem cells.Nature communications · 2026Article
- GPSeq maps the radial organization of eukaryotic genomes along the nuclear periphery-center axis.Nature protocols · 2026Review
- NANOG governs cell metabolism and redox homeostasis in human naïve embryonic stem cells.EMBO reports · 2025Article
- 3D Genome Architecture in Stem Cell Lineage Commitment: from Structural Organization to Precision Regulation.Advanced genetics (Hoboken, N.J.) · 2025Review
- Navigating the 3D genome at single-cell resolution: techniques, computation, and mechanistic landscapes.Briefings in bioinformatics · 2025Review
- The nuclear matrix stabilizes primed-specific genes in human pluripotent stem cells.Nature cell biology · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Single-cell 3D genome structure reveals distinct human pluripotent states.Genome biology · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundPluripotent states of embryonic stem cells (ESCs) with distinct transcriptional profiles affect ESC differentiative capacity and therapeutic potential. Although single-cell RNA sequencing has revealed additional subpopulations and specific features of naive and primed human pluripotent stem cells (hPSCs), the underlying mechanisms that regulate their specific transcription and that control their pluripotent states remain elusive.
resultsBy single-cell analysis of high-resolution, three-dimensional (3D) genomic structure, we herein demonstrate that remodeling of genomic structure is highly associated with the pluripotent states of human ESCs (hESCs). The naive pluripotent state is featured with specialized 3D genomic structures and clear chromatin compartmentalization that is distinct from the primed state. The naive pluripotent state is achieved by remodeling the active euchromatin compartment and reducing chromatin interactions at the nuclear center. This unique genomic organization is linked to enhanced chromatin accessibility on enhancers and elevated expression levels of naive pluripotent genes localized to this region. In contradistinction, the primed state exhibits intermingled genomic organization. Moreover, active euchromatin and primed pluripotent genes are distributed at the nuclear periphery, while repressive heterochromatin is densely concentrated at the nuclear center, reducing chromatin accessibility and the transcription of naive genes.
conclusionsOur data provide insights into the chromatin structure of ESCs in their naive and primed states, and we identify specific patterns of modifications in transcription and chromatin structure that might explain the genes that are differentially expressed between naive and primed hESCs. Thus, the inversion or relocation of heterochromatin to euchromatin via compartmentalization is related to the regulation of chromatin accessibility, thereby defining pluripotent states and cellular identity.
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