scholarly journals Reconstruction of cell spatial organization based on ligand-receptor mediated self-assembly

2020 ◽  
Author(s):  
Xianwen Ren ◽  
Guojie Zhong ◽  
Qiming Zhang ◽  
Lei Zhang ◽  
Yujie Sun ◽  
...  
Keyword(s):  
Self Assembly ◽  
Spatial Organization ◽  
Spatial Information ◽  
Cell Types ◽  
Cellular Interaction ◽  
Great Promise ◽  
Cellular Interactions ◽  
Tumor Microenvironments ◽  
Tissue Dissociation

AbstractSingle-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Since cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, here we present CSOmap, a computational strategy to infer cellular interaction from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of tumor microenvironments for multiple cancers and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be widely applicable to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.

scholarly journals Spatial charting of single cell transcriptomes in tissues

2021 ◽  
Author(s):  
Nicholas Navin ◽  
Runmin Wei ◽  
Siyuan He ◽  
Shanshan Bai ◽  
Emi Sei ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Organization ◽  
Spatial Information ◽  
Ductal Carcinoma ◽  
Single Cells ◽  
Cell Types ◽  
Spatial Structures ◽  
Tissue Sections ◽  
Normal Mouse Brain

Single cell RNA sequencing (scRNA-seq) methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, spatial transcriptomics (ST) assays can profile spatial regions in tissue sections, but do not have single cell genomic resolution. Here, we developed a computational approach called SChart, that combines these two datasets to achieve single cell spatial mapping of cell types, cell states and continuous phenotypes. We applied SChart to reconstruct cellular spatial structures in existing datasets from normal mouse brain and kidney tissues to validate our approach. We also performed scRNA-seq and ST experiments on two ductal carcinoma in situ (DCIS) tissues and applied SChart to identify subclones that were restricted to different ducts, and specific T cell states adjacent to the tumor areas. Our data shows that SChart can accurately map single cells in diverse tissue types to resolve their spatial organization into cellular neighborhoods and tissue structures.

scholarly journals Spatial organization of the somatosensory cortex revealed by cyclic smFISH

2018 ◽  
Author(s):  
Simone Codeluppi ◽  
Lars E. Borm ◽  
Amit Zeisel ◽  
Gioele La Manno ◽  
Josina A. van Lunteren ◽  
...  
Keyword(s):  
Single Cell ◽  
Somatosensory Cortex ◽  
Single Molecule ◽  
Spatial Organization ◽  
Spatial Information ◽  
Cell Types ◽  
Cellular Organization ◽  
New Methods ◽  
The Brain

The global efforts towards the creation of a molecular census of the brain using single-cell transcriptomics is generating a large catalog of molecularly defined cell types lacking spatial information. Thus, new methods are needed to map a large number of cell-specific markers simultaneously on large tissue areas. Here, we developed a cyclic single molecule fluorescence in situ hybridization methodology and defined the cellular organization of the somatosensory cortex using markers identified by single-cell transcriptomics.

scholarly journals Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alma Andersson ◽  
Ludvig Larsson ◽  
Linnea Stenbeck ◽  
Fredrik Salmén ◽  
Anna Ehinger ◽  
...  
Keyword(s):  
Spatial Information ◽  
Cell Types ◽  
Interferon Response ◽  
Type I ◽  
Cellular Interactions ◽  
Her2 Positive ◽  
High Resolution Map ◽  
Functional Relevance ◽  
Macrophage Subset ◽  
Treatment And Diagnosis

AbstractIn the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases.

Carbon Nanotubes-Assisted Fabrication of TiO2 Nanocomposite Film for Optimum Electrochromic Application

2014 ◽  
Vol 989-994 ◽  
pp. 789-792
Author(s):  
Shu Ping Liu ◽  
Wei Wang ◽  
Lin Lin Cui ◽  
Hua Nan Guan
Keyword(s):  
Carbon Nanotubes ◽  
Self Assembly ◽  
Multilayer Film ◽  
Great Promise ◽  
Layer By Layer ◽  
Electrochromic Devices ◽  
Optical Contrast ◽  
Coloration Efficiency ◽  
Assembly Method

Electrochromic composite film consisting of TiO2, chitosan (CS) and carbon nanotubes (CNTs) were fabricated on quartz and FTO substrates by the layer-by-layer self-assembly method (LbL). The multilayer film was characterized by UV-vis spectrum, scanning electron microscopy (SEM), cyclic voltammetry (CV) and chronoamperometric (CA) and in situ spectral electrochemicalmeasurements. The composite material shows high electrochromic performance, with the optical contrast of 11.5% and coloration efficiency of 21.7 cm2/C at 800 nm. The results indicate great promise for the TiO2-based film as a potential material in electrochromic devices.

scholarly journals Robust Acquisition of High Resolution Spatial Transcriptomes from Preserved Tissues with Immunofluorescence Based Laser Capture Microdissection

2021 ◽  
Author(s):  
Xiaodan Zhang ◽  
Chuansheng Hu ◽  
Chen Huang ◽  
Ying Wei ◽  
Xiaowei Li ◽  
...  
Keyword(s):  
Laser Capture Microdissection ◽  
Spatial Organization ◽  
Spatial Information ◽  
A Priori ◽  
Rna Degradation ◽  
Spatially Resolved ◽  
Mouse Small Intestine ◽  
Dissociated Cells ◽  
Laser Capture

The functioning of tissues is fundamentally dependent upon not only the phenotypes of the constituent cells but also their spatial organization in the tissue. However, obtaining comprehensive transcriptomic data based on established phenotypes while retaining this spatial information has been challenging. Here we present a general and robust method based on immunofluorescence-guided laser capture microdissection (immuno-LCM-RNAseq) to enable acquisition of finely resolved spatial transcriptomes with as few as tens of cells from snap-frozen or RNAlater-treated tissues, overcoming the long-standing problem of significant RNA degradation during this lengthy process. The efficacy of this approach is exemplified by the characterization of differences at the transcript isoform level between cells at the tip versus the main capillary body of the mouse small intestine lacteal. With the extensive repertoire of phenotype-specific antibodies that are presently available, our method provides a powerful means by which spatially resolved cellular states can be delineated in situ with preserved tissues. Moreover, such high quality spatial transcriptomes defined by immuno-markers can be used to compare with clusters obtained from single-cell RNAseq studies of dissociated cells as well as applied to bead-based spatial transcriptomics approaches that require such information a priori for cell identification.

scholarly journals Efficient Retroelement-Mediated DNA Writing in Bacteria

2020 ◽  
Author(s):  
Fahim Farzadfard ◽  
Nava Gharaei ◽  
Robert J. Citorik ◽  
Timothy K. Lu
Keyword(s):  
Cell Biology ◽  
Genome Engineering ◽  
Spatial Information ◽  
Cellular Interactions ◽  
Bacterial Genomes ◽  
Microbial Genomes ◽  
High Resolution Mapping ◽  
Resolution Mapping ◽  
Cellular Phenotypes

AbstractThe ability to efficiently and dynamically change information stored in genomes would enable powerful strategies for studying cell biology and controlling cellular phenotypes. Current recombineering-mediated DNA writing platforms in bacteria are limited to specific laboratory conditions, often suffer from suboptimal editing efficiencies, and are not suitable for in situ applications. To overcome these limitations, we engineered a retroelement-mediated DNA writing system that enables efficient and precise editing of bacterial genomes without the requirement for target-specific elements or selection. We demonstrate that this DNA writing platform enables a broad range of applications, including efficient, scarless, and cis-element-independent editing of targeted microbial genomes within complex communities, the high-throughput mapping of spatial information and cellular interactions into DNA memory, and the continuous evolution of cellular traits.One Sentence SummaryHighly-efficient, dynamic, and conditional genome writers are engineered for DNA memory, genome engineering, editing microbial communities, high-resolution mapping of cellular connectomes, and modulating cellular evolution.

scholarly journals A spatial atlas of inhibitory cell types in mouse hippocampus

2018 ◽  
Author(s):  
Xiaoyan Qian ◽  
Kenneth D. Harris ◽  
Thomas Hauling ◽  
Dimitris Nicoloutsopoulos ◽  
Ana B. Muñoz-Manchado ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Memory Function ◽  
Expression Patterns ◽  
Ground Truth ◽  
Spatial Arrangement ◽  
Cell Types ◽  
Cell System ◽  
Inhibitory Neurons ◽  
Hippocampal Area

Understanding the function of a tissue requires knowing the spatial organization of its constituent cell types. In the cerebral cortex, single-cell RNA sequencing (scRNA-seq) has revealed the genome-wide expression patterns that define its many, closely related cell types, but cannot reveal their spatial arrangement. Here we introduce probabilistic cell typing by in situ sequencing (pciSeq), an approach that leverages prior scRNA-seq classification to identify cell types using multiplexed in situ RNA detection. We applied this method to map the inhibitory neurons of hippocampal area CA1, a cell system critical for memory function, for which ground truth is available from extensive prior work identifying the laminar organization of subtly differing cell types. Our method confidently identified 16 interneuron classes, in a spatial arrangement closely matching ground truth. This method will allow identifying the spatial organization of fine cell types across the brain and other tissues.

scholarly journals Spatial molecular profiling: platforms, applications and analysis tools

2020 ◽  
Author(s):  
Minzhe Zhang ◽  
Thomas Sheffield ◽  
Xiaowei Zhan ◽  
Qiwei Li ◽  
Donghan M Yang ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Spatial Information ◽  
Molecular Profiling ◽  
Tissue Imaging ◽  
Imaging Data ◽  
Tissue Heterogeneity ◽  
Tissue Dissociation ◽  
Recent Developments ◽  
Spatial Locations

Abstract Molecular profiling technologies, such as genome sequencing and proteomics, have transformed biomedical research, but most such technologies require tissue dissociation, which leads to loss of tissue morphology and spatial information. Recent developments in spatial molecular profiling technologies have enabled the comprehensive molecular characterization of cells while keeping their spatial and morphological contexts intact. Molecular profiling data generate deep characterizations of the genetic, transcriptional and proteomic events of cells, while tissue images capture the spatial locations, organizations and interactions of the cells together with their morphology features. These data, together with cell and tissue imaging data, provide unprecedented opportunities to study tissue heterogeneity and cell spatial organization. This review aims to provide an overview of these recent developments in spatial molecular profiling technologies and the corresponding computational methods developed for analyzing such data.

scholarly journals Automated cell-type classification in intact tissues by single-cell molecular profiling

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Monica Nagendran ◽  
Daniel P Riordan ◽  
Pehr B Harbury ◽  
Tushar J Desai
Keyword(s):  
Single Cell ◽  
Spatial Information ◽  
Housekeeping Genes ◽  
Cell Types ◽  
Molecular Profiling ◽  
Mouse Lung ◽  
Intact Mouse ◽  
Specificity And Sensitivity

A major challenge in biology is identifying distinct cell classes and mapping their interactions in vivo. Tissue-dissociative technologies enable deep single cell molecular profiling but do not provide spatial information. We developed a proximity ligation in situ hybridization technology (PLISH) with exceptional signal strength, specificity, and sensitivity in tissue. Multiplexed data sets can be acquired using barcoded probes and rapid label-image-erase cycles, with automated calculation of single cell profiles, enabling clustering and anatomical re-mapping of cells. We apply PLISH to expression profile ~2900 cells in intact mouse lung, which identifies and localizes known cell types, including rare ones. Unsupervised classification of the cells indicates differential expression of ‘housekeeping’ genes between cell types, and re-mapping of two sub-classes of Club cells highlights their segregated spatial domains in terminal airways. By enabling single cell profiling of various RNA species in situ, PLISH can impact many areas of basic and medical research.

scholarly journals Liquid-crystal organization of liver tissue

2018 ◽  
Author(s):  
Hernán Morales-Navarrete ◽  
Hidenori Nonaka ◽  
André Scholich ◽  
Fabián Segovia-Miranda ◽  
Walter de Back ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Self Assembly ◽  
Liver Tissue ◽  
Spatial Organization ◽  
Structural Model ◽  
Cell Types ◽  
Soft Condensed Matter ◽  
Distinct Cell ◽  
Tissue Geometry ◽  
Organizing Principles

AbstractFunctional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells as generally assumed, since silencing Integrin-ß1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

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