scholarly journals Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Colleen N McLaughlin ◽  
Maria Brbić ◽  
Qijing Xie ◽  
Tongchao Li ◽  
Felix Horns ◽  
...  
Keyword(s):  
Single Cell ◽  
Developmental Stages ◽  
Sensory Modality ◽  
Olfactory Receptors ◽  
Receptor Expression ◽  
Transcriptional Changes ◽  
Single Nucleus ◽  
Cell Type Specific ◽  
Sensory Responses ◽  
And Function

Recognition of environmental cues is essential for the survival of all organisms. Transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory- (ORNs), thermo-, and hygro-sensory neurons at an early developmental and adult stage using single-cell and single-nucleus RNA sequencing. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using receptor expression and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuron types across multiple developmental stages. We found that cell-type-specific transcriptomes partly reflected axon trajectory choices in development and sensory modality in adults. We uncovered stage-specific genes that could regulate the wiring and sensory responses of distinct ORN types. Collectively, our data reveal transcriptomic features of sensory neuron biology and provide a resource for future studies of their development and physiology.

scholarly journals Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila

2020 ◽  
Author(s):  
Colleen N. McLaughlin ◽  
Maria Brbić ◽  
Qijing Xie ◽  
Tongchao Li ◽  
Felix Horns ◽  
...  
Keyword(s):  
Single Cell ◽  
Olfactory Receptor ◽  
Developmental Stages ◽  
Sensory Modality ◽  
Antennal Segment ◽  
Olfactory Receptors ◽  
Olfactory Receptor Neurons ◽  
Receptor Neurons ◽  
Sensory Responses ◽  
And Function

AbstractRecognition of environmental cues is essential for the survival of all organisms. Precise transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory receptor neurons (ORNs), thermosensory and hygrosensory neurons from the third antennal segment at an early developmental and adult stage. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using these receptors and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuronal types across multiple developmental stages. Cell-type-specific transcriptomes, in part, reflected axon trajectory choices in early development and sensory modality in adults. Our analysis also uncovered type-specific and broadly expressed genes that could modulate adult sensory responses. Collectively, our data reveal important transcriptomic features of sensory neuron biology and provides a resource for future studies of their development and physiology.

scholarly journals Single-Cell RNA-Seq of Cisplatin-Treated Adult Stria Vascularis Identifies Cell Type-Specific Regulatory Networks and Novel Therapeutic Gene Targets

2021 ◽  
Vol 14 ◽  
Author(s):  
Ian A. Taukulis ◽  
Rafal T. Olszewski ◽  
Soumya Korrapati ◽  
Katharine A. Fernandez ◽  
Erich T. Boger ◽  
...  
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Stria Vascularis ◽  
Cell Types ◽  
Cellular Level ◽  
Transcriptional Analysis ◽  
Rna Seq ◽  
Transcriptional Responses ◽  
Transcriptional Changes ◽  
Cell Type Specific

The endocochlear potential (EP) generated by the stria vascularis (SV) is necessary for hair cell mechanotransduction in the mammalian cochlea. We sought to create a model of EP dysfunction for the purposes of transcriptional analysis and treatment testing. By administering a single dose of cisplatin, a commonly prescribed cancer treatment drug with ototoxic side effects, to the adult mouse, we acutely disrupt EP generation. By combining these data with single cell RNA-sequencing findings, we identify transcriptional changes induced by cisplatin exposure, and by extension transcriptional changes accompanying EP reduction, in the major cell types of the SV. We use these data to identify gene regulatory networks unique to cisplatin treated SV, as well as the differentially expressed and druggable gene targets within those networks. Our results reconstruct transcriptional responses that occur in gene expression on the cellular level while identifying possible targets for interventions not only in cisplatin ototoxicity but also in EP dysfunction.

scholarly journals Single-cell atlas of progressive supranuclear palsy reveals a distinct hybrid glial cell population

2021 ◽  
Author(s):  
Abhijeet Sharma ◽  
Won-Min Song ◽  
Kurt Farrell ◽  
Kristen Whitney ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Single Cell ◽  
Neurodegenerative Disorder ◽  
Hybrid Cell ◽  
Unfolded Protein ◽  
Homeostatic Function ◽  
Single Nucleus ◽  
Cell Type Specific ◽  
The Unfolded Protein Response ◽  
Protein Response

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder whose molecular complexity at a single cell level has not been evaluated. Here we analyzed 45,559 high quality nuclei from the subthalamic nucleus and associated basal ganglia regions from post-mortem human PSP brains with varying degrees of tau pathology compared to controls (n=3 per group). We identified novel astrocyte-oligodendrocyte hybrid cell populations that overexpress neurotropic factors in conjunction with suppression of the unfolded protein response pathway. Notably, trajectory analysis identified subpopulations of hybrid cells with distinct astrocytic, oligodendrocytic and hybrid molecular states that change from a neuroprotective hybrid cell to an astrocytic cell with impaired homeostatic function in PSP. Our single nucleus transcriptomic data provides insights into the cell-type-specific contributions to the disease for investigating the molecular and cellular basis of PSP

scholarly journals Identification and characterization of distinct cell cycle stages in cardiomyocytes using the FUCCI transgenic system

2021 ◽  
Author(s):  
Marion Baniol ◽  
Francesca Murganti ◽  
Agata Smialowska ◽  
Joni Panula ◽  
Eniko Lazar ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Developmental Stages ◽  
Neonatal Period ◽  
Acid Oxidation ◽  
Cardiomyocyte Proliferation ◽  
Metabolic Switch ◽  
Distinct Cell ◽  
Transcriptional Changes ◽  
Cell Transcriptome

Understanding the regulatory mechanism by which cardiomyocyte proliferation transitions to endoreplication and cell cycle arrest during the neonatal period is crucial for identifying proproliferative factors and developing regenerative therapies. We used a transgenic mouse model based on the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system to isolate and characterize cycling cardiomyocytes at different cell cycle stages at a single-cell resolution. Single-cell transcriptome analysis of cycling and noncycling cardiomyocytes was performed at postnatal days 0 (P0) and 7 (P7). The FUCCI system proved to be efficient for the identification of cycling cardiomyocytes with the highest mitotic activity at birth, followed by a gradual decline in the number of cycling and mitotic cardiomyocytes during the neonatal period. Cardiomyocytes showed premature cell cycle exit at G1/S shortly after birth and delayed G1/S progression during endoreplication at P7. Single-cell RNA-seq confirmed previously described signaling pathways involved in cardiomyocyte proliferation (Erbb2 and Hippo/YAP), cardiomyocyte motility, and maturation-related transcriptional changes during postnatal development, including the metabolic switch from glycolysis to fatty acid oxidation in cardiomyocytes. Additionally, we generated transcriptional profiles specific to cell division and endoreplication in cardiomyocytes. Deciphering transcriptional changes at different developmental stages and in a cell cycle-specific manner may facilitate the identification of genes important for adult cardiomyocyte proliferation and heart regeneration.

scholarly journals Lung at a Glance: an integrative web toolset of lung ontology, imaging and single cell omics

2020 ◽  
Author(s):  
Yina Du ◽  
Weichen Ouyang ◽  
Joseph A Kitzmiller ◽  
Minzhe Guo ◽  
Shuyang Zhao ◽  
...  
Keyword(s):  
Single Cell ◽  
Knowledge Integration ◽  
Specific Gene ◽  
Imaging Data ◽  
Related Data ◽  
Lung Histology ◽  
Confocal Images ◽  
Cell Type Specific ◽  
Resolution Imaging ◽  
And Function

ABSTRACTRecent advances in single-cell omics and high-resolution imaging have provided unanticipated data resources for the elucidation of genes underlying the complex biological processes critical for organ formation and function. However, processing and integrating large amounts of single-cell omics and imaging data presents a major challenge for most researchers. There is a critical need for ready-to-use computational tools for data/knowledge integration and visualization. Here we present “Lung-at-a-glance”, an easy-to-use web toolset for visualizing and interoperating complex omics and imaging data, providing an interactive web interface to bridge lung anatomic ontology classifications to lung histology and immunofluorescence confocal images, and cell-type-specific gene expression. “Lung-at-a-glance” contains three interactive components: 1) “Region at a glance”, 2) “Cell at a glance” and 3) “Gene at a glance”. “Lung-at-a-glance” and other newly developed web tools for lung-related data query, integration and visualization are publicly available on LGEA web portal v3 https://research.cchmc.org/pbge/lunggens/mainportal.html.

scholarly journals Spatiotemporal mapping of RNA editing in the developing mouse brain using in situ sequencing reveals regional and cell-type-specific regulation

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Elin Lundin ◽  
Chenglin Wu ◽  
Albin Widmark ◽  
Mikaela Behm ◽  
Jens Hjerling-Leffler ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Editing ◽  
Mouse Brain ◽  
Developmental Stages ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Type Specific ◽  
Specific Regulation

Abstract Background Adenosine-to-inosine (A-to-I) RNA editing is a process that contributes to the diversification of proteins that has been shown to be essential for neurotransmission and other neuronal functions. However, the spatiotemporal and diversification properties of RNA editing in the brain are largely unknown. Here, we applied in situ sequencing to distinguish between edited and unedited transcripts in distinct regions of the mouse brain at four developmental stages, and investigate the diversity of the RNA landscape. Results We analyzed RNA editing at codon-altering sites using in situ sequencing at single-cell resolution, in combination with the detection of individual ADAR enzymes and specific cell type marker transcripts. This approach revealed cell-type-specific regulation of RNA editing of a set of transcripts, and developmental and regional variation in editing levels for many of the targeted sites. We found increasing editing diversity throughout development, which arises through regional- and cell type-specific regulation of ADAR enzymes and target transcripts. Conclusions Our single-cell in situ sequencing method has proved useful to study the complex landscape of RNA editing and our results indicate that this complexity arises due to distinct mechanisms of regulating individual RNA editing sites, acting both regionally and in specific cell types.

scholarly journals Quantitative single cell 5hmC sequencing reveals non-canonical gene regulation by non-CG hydroxymethylation

2021 ◽  
Author(s):  
Emily B. Fabyanic ◽  
Peng Hu ◽  
Qi Qiu ◽  
Kiara N. Berrios ◽  
Jennifer Flournoy ◽  
...  
Keyword(s):  
Single Cell ◽  
Bisulfite Sequencing ◽  
Single Cells ◽  
Oxidative Modification ◽  
Biological Processes ◽  
Single Nucleus ◽  
Cell Type Specific ◽  
Gene Regulatory ◽  
Regulatory Functions

Oxidative modification of 5-methylcytosine (5mC) generates 5-hydroxymethylcytosine (5hmC), a DNA modification that exhibits unique epigenetic regulatory functions and impacts diverse biological processes. However, standard single-nucleus/cell bisulfite sequencing methods cannot resolve the base ambiguity between 5mC and 5hmC to accurately measure cell-type specific epigenomic patterns and gene regulatory functions of 5hmC or true 5mC. Here, we develop single-nucleus 5hmC sequencing (snhmC-seq) for quantitative and unbiased 5hmC profiling in single cells by harnessing differential deaminase activity of APOBEC3A towards 5mC and chemically protected 5hmC. We used snhmC-seq to profile single nuclei from cryopreserved mouse brain samples to reveal epigenetic heterogeneity of 5hmC at single-cell resolution and uncovered a non-canonical gene regulatory role of genic 5hmC in non-CG context.

scholarly journals Dynamic changes in the regulatory T-cell heterogeneity and function by murine IL-2 mutein

2020 ◽  
Vol 3 (5) ◽  
pp. e201900520 ◽  
Author(s):  
Daniel R Lu ◽  
Hao Wu ◽  
Ian Driver ◽  
Sarah Ingersoll ◽  
Sue Sohn ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Expression Profiles ◽  
Control Cell ◽  
Mutant Form ◽  
Rna Seq ◽  
Dynamic Changes ◽  
Cell Clustering ◽  
Transcriptional Changes ◽  
And Function

The therapeutic expansion of Foxp3+ regulatory T cells (Tregs) shows promise for treating autoimmune and inflammatory disorders. Yet, how this treatment affects the heterogeneity and function of Tregs is not clear. Using single-cell RNA-seq analysis, we characterized 31,908 Tregs from the mice treated with a half-life extended mutant form of murine IL-2 (IL-2 mutein, IL-2M) that preferentially expanded Tregs, or mouse IgG Fc as a control. Cell clustering analysis revealed that IL-2M specifically expands multiple sub-states of Tregs with distinct expression profiles. TCR profiling with single-cell analysis uncovered Treg migration across tissues and transcriptional changes between clonally related Tregs after IL-2M treatment. Finally, we identified IL-2M–expanded Tnfrsf9+Il1rl1+ Tregs with superior suppressive function, highlighting the potential of IL-2M to expand highly suppressive Foxp3+ Tregs.

scholarly journals SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data

2021 ◽  
Vol 18 (9) ◽  
pp. 1056-1059
Author(s):  
Miao Yu ◽  
Armen Abnousi ◽  
Yanxiao Zhang ◽  
Guoqiang Li ◽  
Lindsay Lee ◽  
...  
Keyword(s):  
High Resolution ◽  
Single Cell ◽  
Target Genes ◽  
Embryonic Stem ◽  
Cell Type ◽  
Computational Tools ◽  
Chromatin Loops ◽  
Chromatin Architecture ◽  
Single Nucleus ◽  
Cell Type Specific

AbstractSingle-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.

scholarly journals Cell transcriptomic atlas of the non-human primate Macaca fascicularis

2021 ◽  
Author(s):  
Lei Han ◽  
Xiaoyu Wei ◽  
Chuanyu Liu ◽  
Giacomo Volpe ◽  
Zhenkun Zhuang ◽  
...  
Keyword(s):  
Single Cell ◽  
Macaca Fascicularis ◽  
Large Scale ◽  
Cell Interaction ◽  
The Body ◽  
Tissue Composition ◽  
Human Genetic Disease ◽  
Single Nucleus ◽  
And Function ◽  
Human Primate

Studying tissue composition and function in non-human primates (NHP) is crucial to understand the nature of our own species. Here, we present a large-scale single-cell and single-nucleus transcriptomic atlas encompassing over one million cells from 43 tissues from the adult NHP Macaca fascicularis. This dataset provides a vast, carefully annotated, resource to study a species phylogenetically close to humans. As proof of principle, we have reconstructed the cell-cell interaction networks driving Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases and intersected our data with human genetic disease orthologous coordinates to identify both expected and unexpected associations. Our Macaca fascicularis cell atlas constitutes an essential reference for future single-cell studies in human and NHP.

Sign in / Sign up

Export Citation Format

Share Document