scholarly journals Semi-automated three-dimensional reconstructions of individual neurons reveal cell type-specific circuits in cortex

2011 ◽  
Vol 4 (4) ◽  
pp. 486-488 ◽  
Author(s):  
Zimbo S.R.M. Boudewijns ◽  
Tatjana Kleele ◽  
Huibert D. Mansvelder ◽  
Bert Sakmann ◽  
Christiaan P.J. de Kock ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals MSTD: an efficient method for detecting multi-scale topological domains from symmetric and asymmetric 3D genomic maps

2018 ◽  
Author(s):  
Yusen Ye ◽  
Lin Gao ◽  
Shihua Zhang
Keyword(s):  
Efficient Method ◽  
Three Dimensional ◽  
Cell Types ◽  
Cell Type ◽  
Range Interaction ◽  
Distinct Cell Type ◽  
Chromosome Conformation ◽  
Topological Domains ◽  
Multi Scale ◽  
Cell Type Specific

AbstractThe chromosome conformation capture (3C) technique and its variants have been employed to reveal the existence of a hierarchy of structures in three-dimensional (3D) chromosomal architecture, including compartments, topologically associating domains (TADs), sub-TADs and chromatin loops. However, existing methods for domain detection were only designed based on symmetric Hi-C maps, ignoring long-range interaction structures between domains. To this end, we proposed a generic and efficient method to identify multi-scale topological domains (MSTD), including cis- and trans-interacting regions, from a variety of 3D genomic datasets. We first applied MSTD to detect promoter-anchored interaction domains (PADs) from promoter capture Hi-C datasets across 17 primary blood cell types. The boundaries of PADs are significantly enriched with one or the combination of multiple epigenetic factors. Moreover, PADs between functionally similar cell types are significantly conserved in terms of domain regions and expression states. Cell type-specific PADs involve in distinct cell type-specific activities and regulatory events by dynamic interactions within them. We also employed MSTD to define multi-scale domains from typical symmetric Hi-C datasets and illustrated its distinct superiority to the-state-of-art methods in terms of accuracy, flexibility and efficiency.

scholarly journals Convergence of dispersed regulatory mutations predicts driver genes in prostate cancer

2016 ◽  
Author(s):  
Richard C. Sallari ◽  
Nicholas A. Sinnott-Armstrong ◽  
Juliet D. French ◽  
Ken J. Kron ◽  
Jason Ho ◽  
...  
Keyword(s):  
High Frequency ◽  
Three Dimensional ◽  
Low Frequency ◽  
Cell Type ◽  
Driver Genes ◽  
Normal Prostate ◽  
Regulatory Mutations ◽  
Cell Type Specific ◽  
Gene Regulatory ◽  
Upregulated Genes

ABSTRACTCancer sequencing predicts driver genes using recurrent protein-altering mutations, but detecting recurrence for non-coding mutations remains unsolved. Here, we present a convergence framework for recurrence analysis of non-coding mutations using three-dimensional co-localization of epigenomically-identified regions. We define the regulatory plexus of each gene as its cell-type-specific three-dimensional gene-regulatory neighborhood, inferred using Hi-C chromosomal interactions and chromatin state annotations. Using 16 matched tumor-normal prostate transcriptomes, we predict tumor-upregulated genes, and find enriched plexus mutations in distal regulatory regions normally repressed in prostate, suggesting out-of-context de-repression. Using 55 matched tumor-normal prostate genomes, we predict 15 driver genes by convergence of dispersed, low-frequency mutations into high-frequency dysregulation events along prostate-specific plexi, while controlling for mutational heterogeneity across regions, chromatin states, and patients. These putative drivers play roles in growth signaling, immune evasion, mitochondrial function, and vascularization, suggesting higher-order pathway-level convergence. We experimentally validate the PLCB4 plexus and its ability to affect the canonical PI3K cancer pathway.

scholarly journals STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing

2021 ◽  
Author(s):  
Dongqing Sun ◽  
Yihan Xiao ◽  
Zhaoyang Liu ◽  
Taiwen Li ◽  
Qiu Wu ◽  
...  
Keyword(s):  
Single Cell ◽  
Three Dimensional ◽  
Cell Types ◽  
Computational Method ◽  
Cellular Heterogeneity ◽  
Integrated Analysis ◽  
Cell Type ◽  
Specificity And Sensitivity ◽  
Cell Type Specific ◽  
Spatial Locations

AbstractThe recent advances in spatial transcriptomics have brought unprecedented opportunities to understand the cellular heterogeneity in the spatial context. However, the current limitations of spatial technologies hamper the exploration of cellular localizations and interactions at single-cell level. Here, we present spatial transcriptomics deconvolution by topic modeling (STRIDE), a computational method to decompose cell-types from spatial mixtures by leveraging topic profiles trained from single-cell transcriptomics. STRIDE accurately estimated the cell-type proportions and showed balanced specificity and sensitivity compared to existing methods. We demonstrate STRIDE’s utility by applying it to different spatial platforms and biological systems. Deconvolution by STRIDE not only mapped rare cell-types to spatial locations but also improved the identification of spatial localized genes and domains. Moreover, topics discovered by STRIDE were associated with cell-type-specific functions, and could be further used to integrate successive sections and reconstruct the three-dimensional architecture of tissues. Taken together, STRIDE is a versatile and extensible tool for integrated analysis of spatial and single-cell transcriptomics and is publicly available at https://github.com/DongqingSun96/STRIDE.

scholarly journals Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex

2011 ◽  
Vol 22 (10) ◽  
pp. 2375-2391 ◽  
Author(s):  
Marcel Oberlaender ◽  
Christiaan P. J. de Kock ◽  
Randy M. Bruno ◽  
Alejandro Ramirez ◽  
Hanno S. Meyer ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Cell Type ◽  
Three Dimensional Structure ◽  
Cell Type Specific

scholarly journals Three-dimensional spatial transcriptomics uncovers cell type dynamics in the rheumatoid arthritis synovium

2020 ◽  
Author(s):  
Sanja Vickovic ◽  
Denis Schapiro ◽  
Konstantin Carlberg ◽  
Britta Lötstedt ◽  
Ludvig Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Three Dimensional ◽  
Cell Types ◽  
Molecular Profiling ◽  
Rheumatoid Arthritis Synovium ◽  
Cellular Interactions ◽  
Rna Seq ◽  
Cell Type ◽  
Multiple Cell ◽  
Cell Type Specific

AbstractThe inflamed rheumatic joint is a highly heterogeneous and complex tissue with dynamic recruitment and expansion of multiple cell types that interact in multifaceted ways within a localized area. Rheumatoid arthritis synovium has primarily been studied either by immunostaining or by molecular profiling after tissue homogenization. Here, we use Spatial Transcriptomics to study local cellular interactions at the site of chronic synovial inflammation. We report comprehensive spatial RNA-seq data coupled to quantitative and cell type-specific chemokine-driven dynamics at and around organized structures of infiltrating leukocyte cells in the synovium.

scholarly journals Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk

Science ◽  
2018 ◽  
Vol 362 (6420) ◽  
pp. eaat4311 ◽  
Author(s):  
Prashanth Rajarajan ◽  
Tyler Borrman ◽  
Will Liao ◽  
Nadine Schrode ◽  
Erin Flaherty ◽  
...  
Keyword(s):  
Neural Progenitor Cells ◽  
Disease Risk ◽  
Three Dimensional ◽  
Cell Type ◽  
Contact Map ◽  
Developmentally Regulated ◽  
Risk Variants ◽  
Cell Type Specific ◽  
Spatial Genome Organization ◽  
Developmental Remodeling

To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type–specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type–specific disease risk vulnerabilities in spatial genome organization.

scholarly journals Deeply hidden genome organization directly mediated by SATB1

2021 ◽  
Author(s):  
Yoshinori Kohwi ◽  
Mari Grange ◽  
Hunter W Richards ◽  
Ya-Chen Liang ◽  
Cheng-Ming Chuong ◽  
...  
Keyword(s):  
Genome Organization ◽  
Three Dimensional ◽  
Ctcf Binding ◽  
Specific Gene ◽  
Genome Architecture ◽  
Cell Type ◽  
Topologically Associated Domains ◽  
Chromatin Folding ◽  
Cell Type Specific ◽  
Cellular Phenotypes

Mammalian genomes are organized by multi-layered chromatin folding. Whether and how three-dimensional genome organization contributes to cell-type specific transcription remains unclear. Here we uncover genome architecture formed by specialized sequences, base-unpairing regions (BURs), bound to a nuclear architectural protein, SATB1. SATB1 regulates cell-type specific transcription that underlies changes in cellular phenotypes. We developed a modified ChIP-seq protocol that stringently purifies genomic DNA only with its directly-associated proteins and unmasked previously-hidden BURs as direct SATB1 targets genome-wide. These SATB1-bound BURs are mutually exclusive from CTCF binding sites, and SATB1 is dispensable for CTCF/cohesion-mediated topologically associated domains (TADs). Instead, BURs largely overlap with lamina associated domains (LADs), and the fraction of BURs tethered to the SATB1 protein network in the nuclear interior is cell type-dependent. Our results reveal TAD-independent chromatin folding mediated by BUR sequences, which serve as genome architecture landmarks targeted by SATB1, to regulate cell-type specific gene expression.

scholarly journals Enhancer dependence of cell-type–specific gene expression increases with developmental age

2020 ◽  
Vol 117 (35) ◽  
pp. 21450-21458 ◽  
Author(s):  
Wenqing Cai ◽  
Jialiang Huang ◽  
Qian Zhu ◽  
Bin E. Li ◽  
Davide Seruggia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Three Dimensional ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Embryonic Cells ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation ◽  
Highly Correlated

How overall principles of cell-type–specific gene regulation (the “logic”) may change during ontogeny is largely unexplored. We compared transcriptomic, epigenomic, and three-dimensional (3D) genomic profiles in embryonic (EryP) and adult (EryD) erythroblasts. Despite reduced chromatin accessibility compared to EryP, distal chromatin of EryD is enriched in H3K27ac, Gata1, and Myb occupancy. EryP-/EryD-shared enhancers are highly correlated with red blood cell identity genes, whereas cell-type–specific regulation employs differentciselements in EryP and EryD cells. In contrast to EryP-specific genes, which exhibit promoter-centric regulation through Gata1, EryD-specific genes rely more on distal enhancers for regulation involving Myb-mediated enhancer activation. Gata1 HiChIP demonstrated an overall increased enhancer–promoter interactions at EryD-specific genes, whereas genome editing in selected loci confirmed distal enhancers are required for gene expression in EryD but not in EryP. Applying a metric for enhancer dependence of transcription, we observed a progressive reliance on cell-specific enhancers with increasing ontogenetic age among diverse tissues of mouse and human origin. Our findings highlight fundamental and conserved differences at distinct developmental stages, characterized by simpler promoter-centric regulation of cell-type–specific genes in embryonic cells and increased combinatorial enhancer-driven control in adult cells.

scholarly journals The three-dimensional chromatin structure of the major human pancreatic cell types reveals lineage-specific regulatory architecture of T2D risk

2021 ◽  
Author(s):  
Su Chun ◽  
Long Gao ◽  
Catherine L May ◽  
James A Pippin ◽  
Keith Boehm ◽  
...  
Keyword(s):  
Single Cell ◽  
Target Genes ◽  
Genetic Diseases ◽  
Three Dimensional ◽  
Specific Gene ◽  
Cell Type ◽  
Pancreatic Cell ◽  
Regulatory Architecture ◽  
Cell Type Specific ◽  
Gene Regulatory

Three-dimensional (3D) chromatin organization maps help to dissect cell type-specific gene regulatory programs. Furthermore, 3D chromatin maps have contributed to elucidating the pathogenesis of complex genetic diseases by connecting distal regulatory regions and genetic risk variants to their respective target genes. To understand the cell type-specific regulatory architecture of diabetes risk, we generated transcriptomic and 3D epigenomic profiles of human pancreatic acinar, alpha, and beta cells using single-cell RNA-seq, single-cell ATAC-seq, and high-resolution Hi-C of sorted cells. Comparisons of these profiles revealed differential A/B (open/closed) chromatin compartmentalization, chromatin looping, and control of cell type-specific gene regulatory programs. We identified a total of 1,094 putative causal-variant-target-gene pairs at 129 type 2 diabetes GWAS signals using pancreatic 3D chromatin maps. We found that the connections between candidate causal variants and their putative target effector genes are cell-type stratified and emphasize previously underappreciated roles for alpha and acinar cells in diabetes pathogenesis

scholarly journals Three-dimensional axon morphologies of individual layer 5 neurons indicate cell type-specific intracortical pathways for whisker motion and touch

2011 ◽  
Vol 108 (10) ◽  
pp. 4188-4193 ◽  
Author(s):  
M. Oberlaender ◽  
Z. S. R. M. Boudewijns ◽  
T. Kleele ◽  
H. D. Mansvelder ◽  
B. Sakmann ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Cell Type ◽  
Individual Layer ◽  
Cell Type Specific
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