scholarly journals ‘Chromatic’ Neuronal Jamming in a Primitive Brain

2018 ◽  
Author(s):  
Margarita Khariton ◽  
Xian Kong ◽  
Jian Qin ◽  
Bo Wang
Keyword(s):  
Cell Types ◽  
Physical Contact ◽  
Specific Interactions ◽  
Cell Type ◽  
Cell Diversity ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
Inanimate Matter ◽  
The Brain ◽  
Jammed State

ABSTRACTJamming models developed in inanimate matter have been widely used to describe cell packing in tissues1–7, but predominantly neglect cell diversity, despite its prevalence in biology. Most tissues, animal brains in particular, comprise a mix of many cell types, with mounting evidence suggesting that neurons can recognize their respective types as they organize in space8–11. How cell diversity revises the current jamming paradigm is unknown. Here, in the brain of the flatworm planarian Schmidtea mediterranea, which exhibits remarkable tissue plasticity within a simple, quantifiable nervous system12–16, we identify a distinct packing state, ‘chromatic’ jamming. Combining experiments with computational modeling, we show that neurons of distinct types form independent percolating networks barring any physical contact. This jammed state emerges as cell packing configurations become constrained by cell type-specific interactions and therefore may extend to describe cell packing in similarly complex tissues composed of multiple cell types.

scholarly journals The Expanding Cell Diversity of the Brain Vasculature

2020 ◽  
Vol 11 ◽  
Author(s):  
Jayden M. Ross ◽  
Chang Kim ◽  
Denise Allen ◽  
Elizabeth E. Crouch ◽  
Kazim Narsinh ◽  
...  
Keyword(s):  
Regional Blood Flow ◽  
Cell Types ◽  
Brain Health ◽  
Vascular Cell ◽  
Brain Vasculature ◽  
Genomic Technologies ◽  
Cell Diversity ◽  
Cell Type Specific ◽  
Neurologic Function ◽  
The Brain

The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood–brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells—including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.

scholarly journals Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain

2021 ◽  
Author(s):  
Sruti Rayaprolu ◽  
Sara Bitarafan ◽  
Ranjita Betarbet ◽  
Sydney N Sunna ◽  
Lihong Cheng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neurological Diseases ◽  
Neuronal Cell ◽  
Cell Types ◽  
Proteomic Profiling ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
The Brain

Isolation and proteomic profiling of brain cell types, particularly neurons, pose several technical challenges which limit our ability to resolve distinct cellular phenotypes in neurological diseases. Therefore, we generated a novel mouse line that enables cell type-specific expression of a biotin ligase, TurboID, via Cre-lox strategy for in vivo proximity-dependent biotinylation of proteins. Using adenoviral-based and transgenic approaches, we show striking protein biotinylation in neuronal cell bodies and axons throughout the mouse brain. We quantified more than 2,000 neuron-derived proteins following enrichment that mapped to numerous subcellular compartments. Synaptic, transmembrane transporters, ion channel subunits, and disease-relevant druggable targets were among the most significantly enriched proteins. Remarkably, we resolved brain region-specific proteomic profiles of Camk2a neurons with distinct functional molecular signatures and disease associations that may underlie regional neuronal vulnerability. Leveraging the neuronal specificity of this in vivo biotinylation strategy, we used an antibody-based approach to uncover regionally unique patterns of neuron-derived signaling phospho-proteins and cytokines, particularly in the cortex and cerebellum. Our work provides a proteomic framework to investigate cell type-specific mechanisms driving physiological and pathological states of the brain as well as complex tissues beyond the brain.

scholarly journals Transposon-mediated, cell type-specific transcription factor recording in the mouse brain

2019 ◽  
Author(s):  
Alexander J. Cammack ◽  
Arnav Moudgil ◽  
Tomas Lagunas ◽  
Michael J. Vasek ◽  
Mark Shabsovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Mouse Tissue ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Cell Type Specific ◽  
The Brain

AbstractTranscription factors (TFs) play a central role in the regulation of gene expression, controlling everything from cell fate decisions to activity dependent gene expression. However, widely-used methods for TF profiling in vivo (e.g. ChIP-seq) yield only an aggregated picture of TF binding across all cell types present within the harvested tissue; thus, it is challenging or impossible to determine how the same TF might bind different portions of the genome in different cell types, or even to identify its binding events at all in rare cell types in a complex tissue such as the brain. Here we present a versatile methodology, FLEX Calling Cards, for the mapping of TF occupancy in specific cell types from heterogenous tissues. In this method, the TF of interest is fused to a hyperactive piggyBac transposase (hypPB), and this bipartite gene is delivered, along with donor transposons, to mouse tissue via a Cre-dependent adeno-associated virus (AAV). The fusion protein is expressed in Cre-expressing cells where it inserts transposon “Calling Cards” near to TF binding sites. These transposons permanently mark TF binding events and can be mapped using high-throughput sequencing. Alternatively, unfused hypPB interacts with and records the binding of the super enhancer (SE)-associated bromodomain protein, Brd4. To demonstrate the FLEX Calling Card method, we first show that donor transposon and transposase constructs can be efficiently delivered to the postnatal day 1 (P1) mouse brain with AAV and that insertion profiles report TF occupancy. Then, using a Cre-dependent hypPB virus, we show utility of this tool in defining cell type-specific TF profiles in multiple cell types of the brain. This approach will enable important cell type-specific studies of TF-mediated gene regulation in the brain and will provide valuable insights into brain development, homeostasis, and disease.

scholarly journals Cell type-specific aging clocks to quantify aging and rejuvenation in regenerative regions of the brain

2022 ◽  
Author(s):  
Matthew T Buckley ◽  
Eric Sun ◽  
Benson M. George ◽  
Ling Liu ◽  
Nicholas Schaum ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Rna Seq ◽  
Cell Type ◽  
Cell Level ◽  
Transcriptomic Data ◽  
Precise Quantification ◽  
Cell Type Specific ◽  
Tissue Aging ◽  
The Brain

Aging manifests as progressive dysfunction culminating in death. The diversity of cell types is a challenge to the precise quantification of aging and its reversal. Here we develop a suite of 'aging clocks' based on single cell transcriptomic data to characterize cell type-specific aging and rejuvenation strategies. The subventricular zone (SVZ) neurogenic region contains many cell types and provides an excellent system to study cell-level tissue aging and regeneration. We generated 21,458 single-cell transcriptomes from the neurogenic regions of 28 mice, tiling ages from young to old. With these data, we trained a suite of single cell-based regression models (aging clocks) to predict both chronological age (passage of time) and biological age (fitness, in this case the proliferative capacity of the neurogenic region). Both types of clocks perform well on independent cohorts of mice. Genes underlying the single cell-based aging clocks are mostly cell-type specific, but also include a few shared genes in the interferon and lipid metabolism pathways. We used these single cell-based aging clocks to measure transcriptomic rejuvenation, by generating single cell RNA-seq datasets of SVZ neurogenic regions for two interventions - heterochronic parabiosis (young blood) and exercise. Interestingly, the use of aging clocks reveals that both heterochronic parabiosis and exercise reverse transcriptomic aging in the niche, but in different ways across cell types and genes. This study represents the first development of high-resolution aging clocks from single cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.

scholarly journals Cell-type-specific alternative polyadenylation (APA) genes reveal the function of dynamic APA in complex tissues

2020 ◽  
Author(s):  
Yulong Bai ◽  
Yidi Qin ◽  
Zhenjiang Fan ◽  
Robert M. Morrison ◽  
KyongNyon Nam ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Cell Type ◽  
Simulation Data ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
Brain Data

ABSTRACTAlternative polyadenylation (APA) causes shortening or lengthening of the 3’-untranslated region (3’-UTR) of genes across multiple cell types. Bioinformatic tools have been developed to identify genes that are affected by APA (APA genes) in single-cell RNA-Seq (scRNA-Seq) data. However, they suffer from low power, and they cannot identify APA genes specific to each cell type (cell-type-specific APA) when multiple cell types are analyzed. To address these limitations, we developed scMAPA that systematically integrates two novel steps. First, scMAPA quantifies 3’-UTR long and short isoforms without requiring assumptions on the read density shape of input data. Second, scMAPA estimates the significance of the APA genes for each cell type while controlling confounders. In the analyses on our novel simulation data and human peripheral blood mono cellular data, scMAPA showed enhanced power in identifying APA genes. Further, in mouse brain data, scMAPA identifies cell-type-specific APA genes, improving interpretability for the cell-type-specific function of APA. We further showed that this improved interpretability helps to understand a novel role of APA on the interaction between neurons and blood vessels, which is critical to maintaining the operational condition of brains. With high sensitivity and interpretability, scMAPA shed novel insights into the function of dynamic APA in complex tissues.Key PointsWe developed a bioinformatic tool, scMAPA, that identifies dynamic APA across multiple cell types and a novel simulation pipeline to assess performance of such tools in APA calling.In simulation data of various scenarios from our novel simulation pipeline, scMAPA achieves sensitivity with a minimal loss of specificity.In human peripheral blood monocellular data, scMAPA identifies APA genes accurately and robustly, finding unique associations of APA with hematological processes.scMAPA identifies APA genes specific to each cell type in mouse brain data while controlling confounders that sheds novel insights into the complex molecular processes.

scholarly journals Multiscale Co-Expression in the Brain

2020 ◽  
Author(s):  
Benjamin D. Harris ◽  
Megan Crow ◽  
Stephan Fischer ◽  
Jesse Gillis
Keyword(s):  
Motor Cortex ◽  
Single Cell ◽  
Rna Sequencing ◽  
Primary Motor Cortex ◽  
Cell Types ◽  
Cell Type ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific ◽  
The Brain ◽  
Regulatory Landscape

ABSTRACTSingle-cell RNA-sequencing (scRNAseq) data can reveal co-regulatory relationships between genes that may be hidden in bulk RNAseq due to cell type confounding. Using the primary motor cortex data from the Brain Initiative Cell Census Network (BICCN), we study cell type specific co-expression across 500,000 cells. Surprisingly, we find that the same gene-gene relationships that differentiate cell types are evident at finer and broader scales, suggesting a consistent multiscale regulatory landscape.

scholarly journals A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the Mouse

2019 ◽  
Author(s):  
◽  
Angela Oliveira Pisco ◽  
Aaron McGeever ◽  
Nicholas Schaum ◽  
Jim Karkanias ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Cellular Processes ◽  
Progressive Loss ◽  
Age Related ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
Molecular Information ◽  
Insight Into

AbstractAging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes which underlie progressive loss of healthy physiology are poorly understood2. To gain a better insight into these processes we have created a single cell transcriptomic atlas across the life span of Mus musculus which includes data from 23 tissues and organs. We discovered cell-specific changes occurring across multiple cell types and organs, as well as age related changes in the cellular composition of different organs. Using single-cell transcriptomic data we were able to assess cell type specific manifestations of different hallmarks of aging, such as senescence3, genomic instability4 and changes in the organism’s immune system2. This Tabula Muris Senis provides a wealth of new molecular information about how the most significant hallmarks of aging are reflected in a broad range of tissues and cell types.

scholarly journals Endothelial cell-type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sweta Parab ◽  
Rachael E Quick ◽  
Ryota L Matsuoka
Keyword(s):  
Vascular Endothelial Cells ◽  
Cell Types ◽  
Vascular Endothelial ◽  
Cell Type ◽  
Vessel Formation ◽  
Brain Vasculature ◽  
Cell Type Specific ◽  
Vessel Development ◽  
The Brain ◽  
Brain Vessel

Vascular endothelial cells (vECs) in the brain exhibit structural and functional heterogeneity. Fenestrated, permeable brain vasculature mediates neuroendocrine function, body-fluid regulation, and neural immune responses; however, its vascular formation remains poorly understood. Here, we show that specific combinations of vascular endothelial growth factors (Vegfs) are required to selectively drive fenestrated vessel formation in the zebrafish myelencephalic choroid plexus (mCP). We found that the combined, but not individual, loss of Vegfab, Vegfc, and Vegfd causes severely impaired mCP vascularization with little effect on neighboring non-fenestrated brain vessel formation, demonstrating fenestrated-vEC-specific angiogenic requirements. This Vegfs-mediated vessel-selective patterning also involves Ccbe1. Expression analyses, cell-type-specific ablation, and paracrine activity-deficient vegfc mutant characterization suggest that vEC-autonomous Vegfc and meningeal fibroblast-derived Vegfab and Vegfd are critical for mCP vascularization. These results define molecular cues and cell types critical for directing fenestrated CP vascularization and indicate that vECs’ distinct molecular requirements for angiogenesis underlie brain vessel heterogeneity.

scholarly journals Three-dimensional spatial transcriptomics uncovers cell type dynamics in the rheumatoid arthritis synovium

2020 ◽  
Author(s):  
Sanja Vickovic ◽  
Denis Schapiro ◽  
Konstantin Carlberg ◽  
Britta Lötstedt ◽  
Ludvig Larsson ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Three Dimensional ◽  
Cell Types ◽  
Molecular Profiling ◽  
Rheumatoid Arthritis Synovium ◽  
Cellular Interactions ◽  
Rna Seq ◽  
Cell Type ◽  
Multiple Cell ◽  
Cell Type Specific

AbstractThe inflamed rheumatic joint is a highly heterogeneous and complex tissue with dynamic recruitment and expansion of multiple cell types that interact in multifaceted ways within a localized area. Rheumatoid arthritis synovium has primarily been studied either by immunostaining or by molecular profiling after tissue homogenization. Here, we use Spatial Transcriptomics to study local cellular interactions at the site of chronic synovial inflammation. We report comprehensive spatial RNA-seq data coupled to quantitative and cell type-specific chemokine-driven dynamics at and around organized structures of infiltrating leukocyte cells in the synovium.

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