scholarly journals A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aaron M Allen ◽  
Megan C Neville ◽  
Sebastian Birtles ◽  
Vincent Croset ◽  
Christoph Daniel Treiber ◽  
...  

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. The relative position of cells along the anterior-posterior axis could also be assigned using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.

Author(s):  
Aaron M. Allen ◽  
Megan C. Neville ◽  
Sebastian Birtles ◽  
Vincent Croset ◽  
Christoph D. Treiber ◽  
...  

AbstractThe Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. Cells could also be assigned to specific neuromeres using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.


2020 ◽  
Author(s):  
Laura E. Mickelsen ◽  
William F. Flynn ◽  
Kristen Springer ◽  
Lydia Wilson ◽  
Eric J. Beltrami ◽  
...  

ABSTRACTThe ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell types in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in a selection of neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit a surprising degree of segregation within neuroanatomical subdivisions of the MB, while genetically-defined MB cell types project topographically to the anterior thalamus. This single cell transcriptomic atlas of cell types in the VPH provides a detailed resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits in health and disease.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Laura E Mickelsen ◽  
William F Flynn ◽  
Kristen Springer ◽  
Lydia Wilson ◽  
Eric J Beltrami ◽  
...  

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance, and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single-cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell populations in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in selected neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit neuroanatomical parcellation within MB subdivisions and topographic projections to the thalamus. This single-cell transcriptomic atlas of VPH cell types provides a resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits.


2021 ◽  
Author(s):  
Periklis Paganos ◽  
Danila Voronov ◽  
Jacob Musser ◽  
Detlev Arendt ◽  
Maria I. Arnone

AbstractIdentifying the molecular fingerprint of organismal cell types is key for understanding their function and evolution. Here, we use single cell RNA sequencing (scRNA-seq) to survey the cell types of the sea urchin early pluteus larva, representing an important developmental transition from non-feeding to feeding larva. We identified 21 distinct cell clusters, representing cells of the digestive, skeletal, immune, and nervous systems. Further subclustering of these revealed a highly detailed portrait of cell diversity across the larva, including the identification of 12 distinct neuronal cell types. Moreover, we corroborated co-expression of key regulatory genes previously shown to drive sea urchin gene regulatory networks, and revealed additional domains in which these regulatory networks are likely to function within the larva. Lastly, we recovered a neuronal cell type co-expressingPdx-1andBrn1/2/4, which had previously been shown to share similar gene expression with vertebrate pancreas. Our results extend this finding, revealing twenty transcription factors shared by this population of neurons in sea urchin and vertebrate pancreatic cells. Using differential expression results from Pdx-1 knockdown experiments, we generate a draft of the Pdx-1 regulatory network in these cells, and hypothesize this network was present in an ancestral deuterostome neuron before being co-opted into the pancreas developmental lineage in vertebrates.


2021 ◽  
Author(s):  
Stephan Fischer ◽  
Jesse Gillis

Our understanding of neuronal cell types has advanced considerably with the publication of single cell atlases, mapping hundreds of putative cell types across brain areas. Characterizing these cell types is a key step towards understanding how the brain works and dysfunctions. Marker genes play an essential role for experimental validation and computational analyses such as physiological characterization through pathway enrichment, annotation, and deconvolution. However, a framework for quantifying marker replicability and picking replicable markers is currently lacking, particularly for cell types at the finest resolution. Here, using high quality data from the Brain Initiative Cell Census Network (BICCN), we systematically investigate marker replicability for the proposed BICCN cell types. We show that, due to dataset-specific noise, we need to combine 5 datasets to obtain robust differentially expressed (DE) genes, particularly for rare populations and lowly expressed genes. We find that two standard DE statistics, fold change and AUROC, can be combined to select the best markers, ranging from highly sensitive to highly specific. Finally, we show that a meta-analytic selection of markers improves performance in downstream computational tasks: cluster separability, annotation and deconvolution. Based on these tasks, we estimate that 10 to 200 meta-analytic markers provide optimal performance, offering an interpretable and robust description of cell types. Replicable marker lists condense single cell atlases into generalizable and accessible information about cell types, opening avenues for multiple downstream applications, including cell type annotation, selection of gene panels and bulk data deconvolution.


2017 ◽  
Author(s):  
Kristofer Davie ◽  
Jasper Janssens ◽  
Duygu Koldere ◽  
Uli Pech ◽  
Sara Aibar ◽  
...  

SummaryThe diversity of cell types and regulatory states in the brain, and how these change during ageing, remains largely unknown. Here, we present a single-cell transcriptome catalogue of the entire adult Drosophila melanogaster brain sampled across its lifespan. Both neurons and glia age through a process of “regulatory erosion”, characterized by a strong decline of RNA content, and accompanied by increasing transcriptional and chromatin noise. We identify more than 50 cell types by specific transcription factors and their downstream gene regulatory networks. In addition to neurotransmitter types and neuroblast lineages, we find a novel neuronal cell state driven by datilografo and prospero. This state relates to neuronal birth order, the metabolic profile, and the activity of a neuron. Our single-cell brain catalogue reveals extensive regulatory heterogeneity linked to ageing and brain function and will serve as a reference for future studies of genetic variation and disease mutations.


2020 ◽  
Author(s):  
August Yue Huang ◽  
Pengpeng Li ◽  
Rachel E. Rodin ◽  
Sonia N. Kim ◽  
Yanmei Dou ◽  
...  

AbstractElucidating the lineage relationships among different cell types is key to understanding human brain development. Here we developed Parallel RNA and DNA analysis after Deep-sequencing (PRDD-seq), which combines RNA analysis of neuronal cell types with analysis of nested spontaneous DNA somatic mutations as cell lineage markers, identified from joint analysis of single cell and bulk DNA sequencing by single-cell MosaicHunter (scMH). PRDD-seq enables the first-ever simultaneous reconstruction of neuronal cell type, cell lineage, and sequential neuronal formation (“birthdate”) in postmortem human cerebral cortex. Analysis of two human brains showed remarkable quantitative details that relate mutation mosaic frequency to clonal patterns, confirming an early divergence of precursors for excitatory and inhibitory neurons, and an “inside-out” layer formation of excitatory neurons as seen in other species. In addition our analysis allows the first estimate of excitatory neuron-restricted precursors (about 10) that generate the excitatory neurons within a cortical column. Inhibitory neurons showed complex, subtype-specific patterns of neurogenesis, including some patterns of development conserved relative to mouse, but also some aspects of primate cortical interneuron development not seen in mouse. PRDD-seq can be broadly applied to characterize cell identity and lineage from diverse archival samples with single-cell resolution and in potentially any developmental or disease condition.Significance StatementStem cells and progenitors undergo a series of cell divisions to generate the neurons of the brain, and understanding this sequence is critical to studying the mechanisms that control cell division and migration in developing brain. Mutations that occur as cells divide are known as the basis of cancer, but have more recently been shown to occur with normal cell divisions, creating a permanent, forensic map of the clonal patterns that define the brain. Here we develop new technology to analyze both DNA mutations and RNA gene expression patterns in single cells from human postmortem brain, allowing us to define clonal patterns among different types of human brain neurons, gaining the first direct insight into how they form.


1970 ◽  
Vol 102 (9) ◽  
pp. 1163-1168 ◽  
Author(s):  
W. D. Seabrook

AbstractSchistocerca gregaria possess four neurones of giant fibre proportions within the abdominal ventral nerve cord. These fibres arise from single cell bodies in the terminal ganglionic mass and pass without interruption to the metathoracic ganglion. Fibres become reduced in diameter when passing through a ganglion. Branching of the giant fibres occurs in abdominal ganglia 6 and 7.


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