scholarly journals A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function

2019 ◽  
Author(s):  
John DeSisto ◽  
Rebecca O’Rourke ◽  
Stephanie Bonney ◽  
Hannah E. Jones ◽  
Fabien Guimiot ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Cell Types ◽  
Multilayered Structure ◽  
Cell Type ◽  
Severe Phenotype ◽  
Secreted Factors ◽  
Extracellular Matrix Components ◽  
And Function ◽  
Insight Into ◽  
Transporter Expression

AbstractThe meninges, a multilayered structure that encases the CNS, is composed mostly of fibroblasts, along with vascular and immune cells. Meningeal fibroblasts are a vital source of signals that control neuronal migration and neurogenesis yet strikingly little is known about their development. We used single cell RNA sequencing to generate a cellular atlas of embryonic meningeal fibroblasts in control and Foxc1-KO mice in which severe CNS defects arise from failed meningeal fibroblast development. We report unique transcriptional signatures for dura, arachnoid and pial fibroblasts and identify S100a6 as the first unique marker of the pial layer. We describe a new meningeal fibroblast subtype marked by µ-Crystallin expression and show these cell types and markers are conserved in human fetal meninges. Our analysis demonstrates layer specific production of extracellular matrix components, transporter expression, and synthesis of secreted factors. Lastly, the cellular atlas of Foxc1-KO meninges provides insight into their severe phenotype, confirming a massive loss in arachnoid and dura fibroblasts and Foxc1-KO pial fibroblasts are so altered that they cluster as a different cell type based on gene expression. These studies provide an unprecedented view of meningeal fibroblast development, highlighting unexpected fibroblast diversity and function, while providing mechanistic insights into the meninges role in CNS development.

scholarly journals Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Amitava Basu ◽  
Vijay K. Tiwari
Keyword(s):  
Regenerative Medicine ◽  
Cell Types ◽  
Direct Conversion ◽  
Cellular Reprogramming ◽  
Specific Cell ◽  
Cell Type ◽  
Pathological Conditions ◽  
Gene Regulatory ◽  
Induced Pluripotent ◽  
And Function

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.

scholarly journals Profound functional and molecular diversity of mitochondria revealed by cell type-specific profiling in vivo

2018 ◽  
Author(s):  
Caroline Fecher ◽  
Laura Trovò ◽  
Stephan A. Müller ◽  
Nicolas Snaidero ◽  
Jennifer Wettmarshausen ◽  
...  
Keyword(s):  
Molecular Diversity ◽  
Molecular Level ◽  
Cell Types ◽  
Long Chain Fatty Acids ◽  
Cell Type ◽  
Mitochondrial Proteome ◽  
Novel Approach ◽  
Cell Type Specific ◽  
And Function

AbstractMitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. Based on predictions from these proteomes, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neurons. Moreover, we identified Rmdn3 as a major determinant of ER-mitochondria proximity in Purkinje cells. Our novel approach enables exploring mitochondrial diversity on the functional and molecular level in many in vivo contexts.

scholarly journals Panoramic stitching of heterogeneous single-cell transcriptomic data

2018 ◽  
Author(s):  
Brian Hie ◽  
Bryan Bryson ◽  
Bonnie Berger
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Data Sets ◽  
Cell Type ◽  
Data Set ◽  
Wide Range ◽  
Data Set Integration ◽  
Biological Patterns ◽  
Insight Into ◽  
Comprehensive Reference

AbstractResearchers are generating single-cell RNA sequencing (scRNA-seq) profiles of diverse biological systems1–4 and every cell type in the human body.5 Leveraging this data to gain unprecedented insight into biology and disease will require assembling heterogeneous cell populations across multiple experiments, laboratories, and technologies. Although methods for scRNA-seq data integration exist6,7, they often naively merge data sets together even when the data sets have no cell types in common, leading to results that do not correspond to real biological patterns. Here we present Scanorama, inspired by algorithms for panorama stitching, that overcomes the limitations of existing methods to enable accurate, heterogeneous scRNA-seq data set integration. Our strategy identifies and merges the shared cell types among all pairs of data sets and is orders of magnitude faster than existing techniques. We use Scanorama to combine 105,476 cells from 26 diverse scRNA-seq experiments across 9 different technologies into a single comprehensive reference, demonstrating how Scanorama can be used to obtain a more complete picture of cellular function across a wide range of scRNA-seq experiments.

scholarly journals Northstar enables automatic classification of known and novel cell types from tumor samples

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fabio Zanini ◽  
Bojk A. Berghuis ◽  
Robert C. Jones ◽  
Benedetta Nicolis di Robilant ◽  
Rachel Yuan Nong ◽  
...  
Keyword(s):  
Cell Types ◽  
Neoplastic Cell ◽  
Computational Approach ◽  
Pancreatic Tumors ◽  
Published Data ◽  
Cell Type ◽  
Disease Heterogeneity ◽  
Manual Task ◽  
Insight Into

Abstract Single cell transcriptomics is revolutionising our understanding of tissue and disease heterogeneity, yet cell type identification remains a partially manual task. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. We developed northstar, a computational approach to classify thousands of cells based on published data within seconds while simultaneously identifying and highlighting new cell states such as malignancies. We tested northstar on data from glioblastoma, melanoma, and seven different healthy tissues and obtained high accuracy and robustness. We collected eleven pancreatic tumors and identified three shared and five private neoplastic cell populations, offering insight into the origins of neuroendocrine and exocrine tumors. Northstar is a useful tool to assign known and novel cell type and states in the age of cell atlases.

scholarly journals Building the right centriole for each cell type

2017 ◽  
Vol 217 (3) ◽  
pp. 823-835 ◽  
Author(s):  
Jadranka Loncarek ◽  
Mónica Bettencourt-Dias
Keyword(s):  
Cell Cycle Progression ◽  
Cell Types ◽  
Cell Type ◽  
Cycle Progression ◽  
Single Organism ◽  
Evolutionarily Conserved ◽  
The Right ◽  
And Function ◽  
The 19Th Century ◽  
High Resolution Microscopy

The centriole is a multifunctional structure that organizes centrosomes and cilia and is important for cell signaling, cell cycle progression, polarity, and motility. Defects in centriole number and structure are associated with human diseases including cancer and ciliopathies. Discovery of the centriole dates back to the 19th century. However, recent advances in genetic and biochemical tools, development of high-resolution microscopy, and identification of centriole components have accelerated our understanding of its assembly, function, evolution, and its role in human disease. The centriole is an evolutionarily conserved structure built from highly conserved proteins and is present in all branches of the eukaryotic tree of life. However, centriole number, size, and organization varies among different organisms and even cell types within a single organism, reflecting its cell type–specialized functions. In this review, we provide an overview of our current understanding of centriole biogenesis and how variations around the same theme generate alternatives for centriole formation and function.

scholarly journals Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function

2021 ◽  
Author(s):  
Alanna G. Spiteri ◽  
Claire L. Wishart ◽  
Roger Pamphlett ◽  
Giuseppe Locatelli ◽  
Nicholas J. C. King
Keyword(s):  
Viral Encephalitis ◽  
Neurological Diseases ◽  
Cell Types ◽  
Cell Type ◽  
Neuroinflammatory Disease ◽  
Experimental Systems ◽  
Immune Mediated ◽  
Experimental Approaches ◽  
And Function ◽  
Disease Specific

AbstractIn neurological diseases, the actions of microglia, the resident myeloid cells of the CNS parenchyma, may diverge from, or intersect with, those of recruited monocytes to drive immune-mediated pathology. However, defining the precise roles of each cell type has historically been impeded by the lack of discriminating markers and experimental systems capable of accurately identifying them. Our ability to distinguish microglia from monocytes in neuroinflammation has advanced with single-cell technologies, new markers and drugs that identify and deplete them, respectively. Nevertheless, the focus of individual studies on particular cell types, diseases or experimental approaches has limited our ability to connect phenotype and function more widely and across diverse CNS pathologies. Here, we critically review, tabulate and integrate the disease-specific functions and immune profiles of microglia and monocytes to provide a comprehensive atlas of myeloid responses in viral encephalitis, demyelination, neurodegeneration and ischemic injury. In emphasizing the differential roles of microglia and monocytes in the severe neuroinflammatory disease of viral encephalitis, we connect inflammatory pathways common to equally incapacitating diseases with less severe inflammation. We examine these findings in the context of human studies and highlight the benefits and inherent limitations of animal models that may impede or facilitate clinical translation. This enables us to highlight common and contrasting, non-redundant and often opposing roles of microglia and monocytes in disease that could be targeted therapeutically.

scholarly journals Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Spatial Organization ◽  
Cell Types ◽  
Gene Promoters ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Insight Into

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

scholarly journals Cell-type-specific promoters for C. elegans glia

2020 ◽  
Author(s):  
Wendy Fung ◽  
Leigh Wexler ◽  
Maxwell G. Heiman
Keyword(s):  
Glial Cell ◽  
Internal State ◽  
Cell Types ◽  
Cell Type ◽  
Sequencing Data ◽  
C Elegans ◽  
External Conditions ◽  
Glial Function ◽  
Cell Type Specific ◽  
And Function

ABSTRACTGlia shape the development and function of the C. elegans nervous system, especially its sense organs and central neuropil (nerve ring). Cell-type-specific promoters allow investigators to label or manipulate individual glial cell types, and therefore provide a key tool for deciphering glial function. In this technical resource, we compare the specificity, brightness, and consistency of cell-type-specific promoters for C. elegans glia. We identify a set of promoters for the study of seven glial cell types (F16F9.3, amphid and phasmid sheath glia; F11C7.2, amphid sheath glia only; grl-2, amphid and phasmid socket glia; hlh-17, cephalic (CEP) sheath glia; and grl-18, inner labial (IL) socket glia) as well as a pan-glial promoter (mir-228). We compare these promoters to promoters that are expressed more variably in combinations of glial cell types (delm-1 and itx-1). We note that the expression of some promoters depends on external conditions or the internal state of the organism, such as developmental stage, suggesting glial plasticity. Finally, we demonstrate an approach for prospectively identifying cell-type-specific glial promoters using existing single-cell sequencing data, and we use this approach to identify two novel promoters specific to IL socket glia (col-53 and col-177).

scholarly journals Structure and mechanism of SARS-CoV-2 Spike N679-V687 deletion variant elucidate cell-type specific evolution of viral fitness

2021 ◽  
Author(s):  
Kapil Gupta ◽  
Christine Toelzer ◽  
Maia Kavanagh Williamson ◽  
Deborah Shoemark ◽  
A. Sofia F. Oliveira ◽  
...  
Keyword(s):  
Cell Types ◽  
Viral Fitness ◽  
Cell Tropism ◽  
Cell Type ◽  
Amino Acid Deletion ◽  
Recognition Motif ◽  
Mechanistic Insight ◽  
Distinct Cell ◽  
Cell Type Specific ◽  
Insight Into

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants which is of particular concern due to their potential for increased transmissibility and pathology. In addition to this entrenched variant diversity in circulation, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation by passaging SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike glycoprotein an eight amino-acid deletion encompassing the furin recognition motif and S1/S2 cleavage site. Here, we analyzed the structure, function and molecular dynamics of this variant spike, providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity, allowing the virus to probe diverse trajectories in distinct cell types to evolve viral fitness.

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.

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