It is now widely appreciated that the spatial organization of the genome is nonrandom, and its complex 3D folding has important consequences for many genome processes. Recent developments in multiplexed, super-resolution microscopy have enabled an unprecedented view of the polymeric structure of chromatin - from the loose folds of whole chromosomes to the detailed loops of cis-regulatory elements that regulate gene expression. Facilitated by the use of robotics, microfluidics, and improved approaches to super-resolution, thousands to hundreds of thousands of individual cells can now be analyzed in an individual experiment. This has led to new insights into the nature of genomic structural features identified by sequencing, such as topologically associated domains (TADs), and the nature of enhancer-promoter interactions underlying transcriptional regulation. We review these recent improvements.
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http://dx.doi.org/10.1016/j.tig.2019.12.010 | DOI Listing |
Cell Discov
January 2025
Biomedical Pioneering Innovation Center (BIOPIC), and School of Life Sciences, Peking University, Beijing, China.
Single-cell three-dimensional (3D) genome techniques have advanced our understanding of cell-type-specific chromatin structures in complex tissues, yet current methodologies are limited in cell throughput. Here we introduce a high-throughput single-cell Hi-C (dscHi-C) approach and its transcriptome co-assay (dscHi-C-multiome) using droplet microfluidics. Using dscHi-C, we investigate chromatin structural changes during mouse brain aging by profiling 32,777 single cells across three developmental stages (3 months, 12 months, and 23 months), yielding a median of 78,220 unique contacts.
View Article and Find Full Text PDFFree Neuropathol
January 2024
NeuroMarkers, Houston, Texas, USA.
Glioblastoma is the most frequent and malignant primary brain tumor. Although the survival is generally dismal for glioblastoma patients, risk stratification and the identification of high-risk subgroups is important for prompt and aggressive management. The G1-G7 molecular subgroup classification based on the MAPK pathway activation has offered for the first time a non-redundant, all-inclusive classification of adult glioblastoma.
View Article and Find Full Text PDFRegen Ther
March 2025
Division of Developmental Biology, Center for Stem Cell & Organoid Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by Yamanaka factors, including pioneer transcription factors (TFs), has greatly reshaped our traditional understanding of cell plasticity and demonstrated the remarkable potential of pioneer TFs. In addition to iPSC reprogramming, pioneer TFs are pivotal in direct reprogramming or transdifferentiation where somatic cells are converted into different cell types without passing through a pluripotent state. Pioneer TFs initiate a reprogramming process through chromatin opening, thereby establishing competence for new gene regulatory programs.
View Article and Find Full Text PDFThe use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Automation, Xiamen University, Xiang'an South Road, Xiang'an, 361102, Xiamen, Fujian, China.
Understanding cell destiny requires unraveling the intricate mechanism of gene regulation, where transcription factors (TFs) play a pivotal role. However, the actual contribution of TFs, that is TF activity, is not only determined by TF expression, but also accessibility of corresponding chromatin regions. Therefore, we introduce BIOTIC, an advanced Bayesian model with a well-established gene regulation structure that harnesses the power of single-cell multi-omics data to model the gene expression process under the control of regulatory elements, thereby defining the regulatory activity of TFs with variational inference.
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