scholarly journals A lineage-resolved molecular atlas of C. elegans embryogenesis at single-cell resolution

Science ◽  
2019 ◽  
Vol 365 (6459) ◽  
pp. eaax1971 ◽  
Author(s):  
Jonathan S. Packer ◽  
Qin Zhu ◽  
Chau Huynh ◽  
Priya Sivaramakrishnan ◽  
Elicia Preston ◽  
...  
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Single Cell ◽  
Molecular Basis ◽  
Cell Types ◽  
Embryonic Cells ◽  
Cell Type ◽  
C Elegans ◽  
Exact Position ◽  
Sister Cells

Caenorhabditis elegans is an animal with few cells but a wide diversity of cell types. In this study, we characterize the molecular basis for their specification by profiling the transcriptomes of 86,024 single embryonic cells. We identify 502 terminal and preterminal cell types, mapping most single-cell transcriptomes to their exact position in C. elegans’ invariant lineage. Using these annotations, we find that (i) the correlation between a cell’s lineage and its transcriptome increases from middle to late gastrulation, then falls substantially as cells in the nervous system and pharynx adopt their terminal fates; (ii) multilineage priming contributes to the differentiation of sister cells at dozens of lineage branches; and (iii) most distinct lineages that produce the same anatomical cell type converge to a homogenous transcriptomic state.

scholarly journals A lineage-resolved molecular atlas of C. elegans embryogenesis at single cell resolution

2019 ◽  
Author(s):  
Jonathan S. Packer ◽  
Qin Zhu ◽  
Chau Huynh ◽  
Priya Sivaramakrishnan ◽  
Elicia Preston ◽  
...  
Keyword(s):  
Single Cell ◽  
Molecular Basis ◽  
Cell Types ◽  
Early Embryo ◽  
Embryonic Cells ◽  
Cell Type ◽  
C Elegans ◽  
Cell Divisions ◽  
Exact Position ◽  
The Relationship

AbstractC. elegans is an animal with few cells, but a striking diversity of cell types. Here, we characterize the molecular basis for their specification by profiling the transcriptomes of 84,625 single embryonic cells. We identify 284 terminal and pre-terminal cell types, mapping most single cell transcriptomes to their exact position in C. elegans’ invariant lineage. We use these annotations to perform the first quantitative analysis of the relationship between lineage and the transcriptome for a whole organism. We find that a strong lineage-transcriptome correlation in the early embryo breaks down in the final two cell divisions as cells adopt their terminal fates and that most distinct lineages that produce the same anatomical cell type converge to a homogenous transcriptomic state. Users can explore our data with a graphical application “VisCello”.

scholarly journals Single-cell RNA profiling links ncRNAs to spatiotemporal gene expression during C. elegans embryogenesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yan Sun ◽  
Qichao Yu ◽  
Lei Li ◽  
Zhanlong Mei ◽  
Biaofeng Zhou ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Specific Protein ◽  
Embryonic Cells ◽  
Cell Type ◽  
Gene Expressions ◽  
Protein Coding ◽  
C Elegans ◽  
Protein Coding Genes ◽  
Cell Type Specific

Abstract Recent studies show that non-coding RNAs (ncRNAs) can regulate the expression of protein-coding genes and play important roles in mammalian development. Previous studies have revealed that during C. elegans (Caenorhabditis elegans) embryo development, numerous genes in each cell are spatiotemporally regulated, causing the cell to differentiate into distinct cell types and tissues. We ask whether ncRNAs participate in the spatiotemporal regulation of genes in different types of cells and tissues during the embryogenesis of C. elegans. Here, by using marker-free full-length high-depth single-cell RNA sequencing (scRNA-seq) technique, we sequence the whole transcriptomes from 1031 embryonic cells of C. elegans and detect 20,431 protein-coding genes, including 22 cell-type-specific protein-coding markers, and 9843 ncRNAs including 11 cell-type-specific ncRNA markers. We induce a ncRNAs-based clustering strategy as a complementary strategy to the protein-coding gene-based clustering strategy for single-cell classification. We identify 94 ncRNAs that have never been reported to regulate gene expressions, are co-expressed with 1208 protein-coding genes in cell type specific and/or embryo time specific manners. Our findings suggest that these ncRNAs could potentially influence the spatiotemporal expression of the corresponding genes during the embryogenesis of C. elegans.

scholarly journals A nervous system-specific subnuclear organelle in Caenorhabditis elegans

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Kenneth Pham ◽  
Neda Masoudi ◽  
Eduardo Leyva-Díaz ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Homeobox Gene ◽  
Cell Types ◽  
Nuclear Bodies ◽  
Loss Of Function ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Splicing Speckles ◽  
Polycomb Bodies

Abstract We describe here phase-separated subnuclear organelles in the nematode Caenorhabditis elegans, which we term NUN (NUclear Nervous system-specific) bodies. Unlike other previously described subnuclear organelles, NUN bodies are highly cell type specific. In fully mature animals, 4–10 NUN bodies are observed exclusively in the nucleus of neuronal, glial and neuron-like cells, but not in other somatic cell types. Based on co-localization and genetic loss of function studies, NUN bodies are not related to other previously described subnuclear organelles, such as nucleoli, splicing speckles, paraspeckles, Polycomb bodies, promyelocytic leukemia bodies, gems, stress-induced nuclear bodies, or clastosomes. NUN bodies form immediately after cell cycle exit, before other signs of overt neuronal differentiation and are unaffected by the genetic elimination of transcription factors that control many other aspects of neuronal identity. In one unusual neuron class, the canal-associated neurons, NUN bodies remodel during larval development, and this remodeling depends on the Prd-type homeobox gene ceh-10. In conclusion, we have characterized here a novel subnuclear organelle whose cell type specificity poses the intriguing question of what biochemical process in the nucleus makes all nervous system-associated cells different from cells outside the nervous system.

scholarly journals Comprehensive characterization of tissue-specific chromatin accessibility in L2 Caenorhabditis elegans nematodes

2020 ◽  
Author(s):  
Timothy J. Durham ◽  
Riza M. Daza ◽  
Louis Gevirtzman ◽  
Darren A. Cusanovich ◽  
William Stafford Noble ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Patterns ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Gene Expression Patterns ◽  
Rna Seq ◽  
Cell Type ◽  
Tissue Specific ◽  
C Elegans

AbstractRecently developed single cell technologies allow researchers to characterize cell states at ever greater resolution and scale. C. elegans is a particularly tractable system for studying development, and recent single cell RNA-seq studies characterized the gene expression patterns for nearly every cell type in the embryo and at the second larval stage (L2). Gene expression patterns are useful for learning about gene function and give insight into the biochemical state of different cell types; however, in order to understand these cell types, we must also determine how these gene expression levels are regulated. We present the first single cell ATAC-seq study in C. elegans. We collected data in L2 larvae to match the available single cell RNA-seq data set, and we identify tissue-specific chromatin accessibility patterns that align well with existing data, including the L2 single cell RNA-seq results. Using a novel implementation of the latent Dirichlet allocation algorithm, we leverage the single-cell resolution of the sci-ATAC-seq data to identify accessible loci at the level of individual cell types, providing new maps of putative cell type-specific gene regulatory sites, with promise for better understanding of cellular differentiation and gene regulation in the worm.

scholarly journals c302: a multiscale framework for modelling the nervous system of Caenorhabditis elegans

2018 ◽  
Vol 373 (1758) ◽  
pp. 20170379 ◽  
Author(s):  
Padraig Gleeson ◽  
David Lung ◽  
Radu Grosu ◽  
Ramin Hasani ◽  
Stephen D. Larson
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
In Silico ◽  
Cell Types ◽  
Neuronal Model ◽  
C Elegans ◽  
Behaviour Modelling ◽  
Cellular Resolution ◽  
High Level ◽  
Crucial Part

The OpenWorm project has the ambitious goal of producing a highly detailed in silico model of the nematode Caenorhabditis elegans . A crucial part of this work will be a model of the nervous system encompassing all known cell types and connections. The appropriate level of biophysical detail required in the neuronal model to reproduce observed high-level behaviours in the worm has yet to be determined. For this reason, we have developed a framework, c302, that allows different instances of neuronal networks to be generated incorporating varying levels of anatomical and physiological detail, which can be investigated and refined independently or linked to other tools developed in the OpenWorm modelling toolchain. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans

2007 ◽  
Vol 3 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Maxwell G. Heiman ◽  
Shai Shaham
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Types ◽  
Neuronal Morphology ◽  
Sensory Organs ◽  
Nematode Caenorhabditis Elegans ◽  
C Elegans

AbstractThe nematode Caenorhabditis elegans has a simple nervous system with glia restricted primarily to sensory organs. Some of the activities that would be provided by glia in the mammalian nervous system are either absent or provided by non-glial cell types in C. elegans, with only a select set of mammalian glial activities being similarly provided by specialized glial cells in this animal. These observations suggest that ancestral roles of glia may be to modulate neuronal morphology and neuronal sensitivity in sensory organs.

A Deficiency Screen for Zygotic Loci Required for Establishment and Patterning of the Epidermis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 185-206 ◽  
Author(s):  
Rebecca M Terns ◽  
Peggy Kroll-Conner ◽  
Jiangwen Zhu ◽  
Sooyoun Chung ◽  
Joel H Rothman
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Epidermal Cells ◽  
Epidermal Differentiation ◽  
Apparent Effect ◽  
Internal Organs ◽  
C Elegans ◽  
Seam Cell ◽  
Genomic Regions ◽  
Caenorhabditis Elegans Genome

To identify genomic regions required for establishment and patterning of the epidermis, we screened 58 deficiencies that collectively delete at least ∼67% of the Caenorhabditis elegans genome. The epidermal pattern of deficiency homozygous embryos was analyzed by examining expression of a marker specific for one of the three major epidermal cell types, the seam cells. The organization of the epidermis and internal organs was also analyzed using a monoclonal antibody specific for epithelial adherens junctions. While seven deficiencies had no apparent effect on seam cell production, 21 were found to result in subnormal, and five in excess numbers of these cells. An additional 23 deficiencies blocked expression of the seam cell marker, in some cases without preventing cell proliferation. Two deficiencies result in multinucleate seam cells. Deficiencies were also identified that result in subnormal numbers of epidermal cells, hyperfusion of epidermal cells into a large syncytium, or aberrant epidermal differentiation. Finally, analysis of internal epithelia revealed deficiencies that cause defects in formation of internal organs, including circularization of the intestine and bifurcation of the pharynx lumen. This study reveals that many regions of the C. elegans genome are required zygotically for patterning of the epidermis and other epithelia.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

scholarly journals Genomic Architecture of Cells in Tissues (GeACT): Study of Human Mid-gestation Fetus

2020 ◽  
Author(s):  
Feng Tian ◽  
Fan Zhou ◽  
Xiang Li ◽  
Wenping Ma ◽  
Honggui Wu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Human Cell ◽  
Expression Profiles ◽  
Single Cells ◽  
Cell Types ◽  
List Type ◽  
Cell Type ◽  
Genomic Architecture ◽  
Gene Modules

SummaryBy circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.HighlightsGenomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetusDetermining correlated gene modules (CGMs) in different cell types by MALBAC-DTMeasuring chromatin open regions in single cells with high detectability by METATACIntegrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM

scholarly journals Mapping single-cell atlases throughout Metazoa unravels cell type evolution

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alexander J Tarashansky ◽  
Jacob M Musser ◽  
Margarita Khariton ◽  
Pengyang Li ◽  
Detlev Arendt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Cell ◽  
Cell Types ◽  
The Self ◽  
Cell Type ◽  
Germ Layers ◽  
Animal Evolution ◽  
Self Assembling ◽  
Animal Phyla ◽  
Cell Data

Comparing single-cell transcriptomic atlases from diverse organisms can elucidate the origins of cellular diversity and assist the annotation of new cell atlases. Yet, comparison between distant relatives is hindered by complex gene histories and diversifications in expression programs. Previously, we introduced the self-assembling manifold (SAM) algorithm to robustly reconstruct manifolds from single-cell data (Tarashansky et al., 2019). Here, we build on SAM to map cell atlas manifolds across species. This new method, SAMap, identifies homologous cell types with shared expression programs across distant species within phyla, even in complex examples where homologous tissues emerge from distinct germ layers. SAMap also finds many genes with more similar expression to their paralogs than their orthologs, suggesting paralog substitution may be more common in evolution than previously appreciated. Lastly, comparing species across animal phyla, spanning mouse to sponge, reveals ancient contractile and stem cell families, which may have arisen early in animal evolution.

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