ArticleGenome biology2021
Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Reference-guided pseudotime inference across species and biological contexts.bioRxiv : the preprint server for biology · 2026Article
- Harmonizing single-cell 3D genome data with STARK and scNucleome.Genome biology · 2026Article
- Sceptic: pseudotime analysis for time-series single-cell sequencing and imaging data.Genome biology · 2025Article
- Unveiling Multi-Scale Architectural Features in Single-Cell Hi-C Data Using scCAFE.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Slow awakening of the silent X chromosome in female primordial germ cells.Nature structural & molecular biology · 2025Article
- Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan.Nature methods · 2025Article
- Integration of scHi-C and scRNA-seq data defines distinct 3D-regulated and biological-context dependent cell subpopulations.Nature communications · 2024Article
- A system to analyze the initiation of random X-chromosome inactivation using time-lapse imaging of single cells.Scientific reports · 2024Article
- GAGE-seq concurrently profiles multiscale 3D genome organization and gene expression in single cells.Nature genetics · 2024Article
- Hi-BDiSCO: folding 3D mesoscale genome structures from Hi-C data using brownian dynamics.Nucleic acids research · 2024Article
- A Lightweight Framework For Chromatin Loop Detection at the Single-Cell Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- [Advances in methods and applications of single-cell Hi-C data analysis].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023Article
- SCOTv2: Single-Cell Multiomic Alignment with Disproportionate Cell-Type Representation.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
- Mapping nucleosome and chromatin architectures: A survey of computational methods.Computational and structural biotechnology journal · 2022Review
- Every gene everywhere all at once: High-precision measurement of 3D chromosome architecture with single-cell Hi-C.Frontiers in molecular biosciences · 2022Review
- X-factors in human disease: impact of gene content and dosage regulation.Human molecular genetics · 2021Review
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14 authors.
Funding
Abstract
backgroundMammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data from these three modalities obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C.
resultsAllele-specific contact decay profiles obtained by single-cell Hi-C clearly show that the inactive X chromosome has a unique profile in differentiated cells that have undergone X inactivation. Loss of this inactive X-specific structure at mitosis is followed by its reappearance during the cell cycle, suggesting a "bookmark" mechanism. Differentiation of embryonic stem cells to follow the onset of X inactivation is associated with changes in contact decay profiles that occur in parallel on both the X chromosomes and autosomes. Single-cell RNA-seq and ATAC-seq show evidence of a delay in female versus male cells, due to the presence of two active X chromosomes at early stages of differentiation. The onset of the inactive X-specific structure in single cells occurs later than gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Single-cell Hi-C highlights evidence of discrete changes in nuclear structure characterized by the acquisition of very long-range contacts throughout the nucleus. Novel computational approaches allow for the effective alignment of single-cell gene expression, chromatin accessibility, and 3D chromosome structure.
conclusionsBased on trajectory analyses, three distinct nuclear structure states are detected reflecting discrete and profound simultaneous changes not only to the structure of the X chromosomes, but also to that of autosomes during differentiation. Our study reveals that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.
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