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Comprehensive single-cell transcriptional profiling of a multicellular organism.

ABSTRACT: To resolve cellular heterogeneity, we developed a combinatorial indexing strategy to profile the transcriptomes of single cells or nuclei, termed sci-RNA-seq (single-cell combinatorial indexing RNA sequencing). We applied sci-RNA-seq to profile nearly 50,000 cells from the nematode Caenorhabditis elegans at the L2 larval stage, which provided >50-fold "shotgun" cellular coverage of its somatic cell composition. From these data, we defined consensus expression profiles for 27 cell types and recovered rare neuronal cell types corresponding to as few as one or two cells in the L2 worm. We integrated these profiles with whole-animal chromatin immunoprecipitation sequencing data to deconvolve the cell type-specific effects of transcription factors. The data generated by sci-RNA-seq constitute a powerful resource for nematode biology and foreshadow similar atlases for other organisms.

SUBMITTER: Cao J

PROVIDER: S-EPMC5894354 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Comprehensive single-cell transcriptional profiling of a multicellular organism.

Cao Junyue J Packer Jonathan S JS Ramani Vijay V Cusanovich Darren A DA Huynh Chau C Daza Riza R Qiu Xiaojie X Lee Choli C Furlan Scott N SN Steemers Frank J FJ Adey Andrew A Waterston Robert H RH Trapnell Cole C Shendure Jay J

Science (New York, N.Y.) 20170801 6352

To resolve cellular heterogeneity, we developed a combinatorial indexing strategy to profile the transcriptomes of single cells or nuclei, termed sci-RNA-seq (single-cell combinatorial indexing RNA sequencing). We applied sci-RNA-seq to profile nearly 50,000 cells from the nematode <i>Caenorhabditis elegans</i> at the L2 larval stage, which provided >50-fold "shotgun" cellular coverage of its somatic cell composition. From these data, we defined consensus expression profiles for 27 cell types an ...[more]

PMID: 28818938

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Project description:Volvocine green algae represent the "evolutionary time machine" model lineage for studying multicellularity, because they encompass the whole range of evolutionary transition of multicellularity from unicellular Chlamydomonas to >500-celled Volvox. Multicellular volvocalean species including Gonium pectorale and Volvox carteri generally have several common morphological features to survive as integrated multicellular organisms such as "rotational asymmetry of cells" so that the cells become components of the individual and "cytoplasmic bridges between protoplasts in developing embryos" to maintain the species-specific form of the multicellular individual before secretion of new extracellular matrix (ECM). However, these morphological features have not been studied in the four-celled colonial volvocine species Tetrabaena socialis that is positioned in the most basal lineage within the colonial or multicellular volvocine greens. Here we established synchronous cultures of T. socialis and carried out immunofluorescence microscopic and ultrastructural observations to elucidate these two morphological attributes. Based on immunofluorescence microscopy, four cells of the mature T. socialis colony were identical in morphology but had rotational asymmetry in arrangement of microtubular rootlets and separation of basal bodies like G. pectorale and V. carteri. Ultrastructural observations clearly confirmed the presence of cytoplasmic bridges between protoplasts in developing embryos of T. socialis even after the formation of new flagella in each daughter protoplast within the parental ECM. Therefore, these two morphological attributes might have evolved in the common four-celled ancestor of the colonial volvocine algae and contributed to the further increase in cell number and complexity of the multicellular individuals of this model lineage. T. socialis is one of the simplest integrated multicellular organisms in which four identical cells constitute the individual.

Project description:BackgroundA convergence of technological breakthroughs in the past decade has facilitated the development of rapid screening tools for biomarkers of toxicant exposure and effect. Platforms using the whole adult organism to evaluate the genome-wide response to toxicants are especially attractive. Recent work demonstrates the feasibility of this approach in vertebrates using the experimentally robust zebrafish model. In the present study, we evaluated gene expression changes in whole adult male zebrafish following an acute 24 hr high dose exposure to three metals with known human health risks. Male adult zebrafish were exposed to nickel chloride, cobalt chloride or sodium dichromate concentrations corresponding to their respective 96 hr LC20, LC40 and LC60. Histopathology was performed on a subset of metal-exposed zebrafish to phenotypically anchor transcriptional changes associated with each metal.ResultsComparative analysis identified subsets of differentially expressed transcripts both overlapping and unique to each metal. Application of gene ontology (GO) and transcription factor (TF) enrichment algorithms revealed a number of key biological processes perturbed by metal poisonings and the master transcriptional regulators mediating gene expression changes. Metal poisoning differentially activated biological processes associated with ribosome biogenesis, proteosomal degradation, and p53 signaling cascades, while repressing oxygen-generating pathways associated with amino acid and lipid metabolism. Despite appreciable effects on gene regulation, nickel poisoning did not induce any morphological alterations in male zebrafish organs and tissues. Histopathological effects of cobalt remained confined to the olfactory system, while chromium targeted the gills, pharynx, and intestinal mucosa. A number of enriched transcription factors mediated the observed gene response to metal poisoning, including known targets such as p53, HIF1α, and the myc oncogene, and novel regulatory factors such as XBP1, GATA6 and HNF3β.ConclusionsThis work uses an experimentally innovative approach to capture global responses to metal poisoning and provides mechanistic insights into metal toxicity.

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Comprehensive single-cell transcriptional profiling of a multicellular organism.

Publications

Comprehensive single-cell transcriptional profiling of a multicellular organism.

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