scholarly journals Epidermal Lamellar Body Biogenesis: Insight Into the Roles of Golgi and Lysosomes

Author(s):  
Sarmistha Mahanty ◽  
Subba Rao Gangi Setty

Epidermal lamellar bodies (eLBs) are secretory organelles that carry a wide variety of secretory cargo required for skin homeostasis. eLBs belong to the class of lysosome-related organelles (LROs), which are cell-type-specific organelles that perform diverse functions. The formation of eLBs is thought to be related to that of other LROs, which are formed either through the gradual maturation of Golgi/endosomal precursors or by the conversion of conventional lysosomes. Current evidence suggests that eLB biogenesis presumably initiate from trans-Golgi network and receive cargo from endosomes, and also acquire lysosome characteristics during maturation. These multistep biogenesis processes are frequently disrupted in human skin disorders. However, many gaps remain in our understanding of eLB biogenesis and their relationship to skin diseases. Here, we describe our current understanding on eLB biogenesis with a focus on cargo transport to this LRO and highlight key areas where future research is needed.

2021 ◽  
Vol 101 (1) ◽  
pp. 353-415
Author(s):  
Jochen F. Staiger ◽  
Carl C. H. Petersen

The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment. Rodents can use their whiskers to detect stimuli, distinguish textures, locate objects and navigate. Important aspects of whisker sensation are thought to result from neuronal computations in the whisker somatosensory cortex (wS1). Each whisker is individually represented in the somatotopic map of wS1 by an anatomical unit named a ‘barrel’ (hence also called barrel cortex). This allows precise investigation of sensory processing in the context of a well-defined map. Here, we first review the signaling pathways from the whiskers to wS1, and then discuss current understanding of the various types of excitatory and inhibitory neurons present within wS1. Different classes of cells can be defined according to anatomical, electrophysiological and molecular features. The synaptic connectivity of neurons within local wS1 microcircuits, as well as their long-range interactions and the impact of neuromodulators, are beginning to be understood. Recent technological progress has allowed cell-type-specific connectivity to be related to cell-type-specific activity during whisker-related behaviors. An important goal for future research is to obtain a causal and mechanistic understanding of how selected aspects of tactile sensory information are processed by specific types of neurons in the synaptically connected neuronal networks of wS1 and signaled to downstream brain areas, thus contributing to sensory-guided decision-making.


2021 ◽  
Vol 10 (12) ◽  
pp. e363101220409
Author(s):  
Mayara Zagoto ◽  
Gabriel Fernando Esteves Cardia ◽  
Edvalkia Magna Teobaldo da Rocha ◽  
Kathia Socorro Mathias Mourão ◽  
Vanderly Janeiro ◽  
...  

Currently, natural products are being used as a therapeutic alternative in the treatment and prevention of several diseases due to their low toxicity and relevant pharmacological potential. Thus, we can highlight basil (Ocimum basilicum L), one of the most used aromatic plants worldwide. Therefore, we provide some current evidence and insight into the potential therapeutic effect of basil essential oil to expand the available knowledge. A narrative review was carried out by searching electronic databases, providing a comprehensive analysis of the literature, where it was possible to identify existing problems and gaps to facilitate future research on basil essential oil. The available literature on basil essential oil presents us with several important pharmacological activities, such as: antioxidant, antiviral, antimicrobial, analgesic, anti-inflammatory, and analgesic and diuretic properties, among others. However, further research must be carried out to increase knowledge about this plant with enormous potential and determine its effectiveness and use in clinical conditions.


2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  

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.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Noritaka Oyama ◽  
Fumio Kaneko

Skin is highly accessible and valuable organ, which holds promise to accelerate the understanding of future medical innovation in association with skin transplantation, engineering, and wound healing. In skin transplantation biology, multistage and multifocal damages occur in both grafted donor and perilesional host skin and need to be repaired properly for the engraftment and maintenance of characteristic skin architecture. These local events are more unlikely to be regulated by the host immunity, because human skin transplantation has accomplished the donor skin engraftment onto the immunocompromised or immunosuppressive animals. Recent studies have emerged the importance of α-smooth muscle actin- (SMA-) positive myofibroblasts, via stage- and cell-specific contribution of TGFβ, PDGF, ET-1, CCN-2 signalling pathways, and mastocyte-derived mediators (e.g., histamine and tryptase), for the functional reorganisation of the grafted skin. Moreover, particular cell lineages from bone marrow (BM) cells have been shown to harbour the diferentiation capacity into multiple skin cell phenotypes, including epidermal keratinocytes and dermal endothelial cells and pericytes, undercontrolled by chemokines or cytokines. From a dermatological viewpoint, we review the recent update of cell-type- and molecular-specific action associated with reconstitution of the grafted skin and also focus on the novel application of BM transplantation medicine in genetic skin diseases.


2019 ◽  
Author(s):  
Divyanshi Srivastava ◽  
Begüm Aydin ◽  
Esteban O. Mazzoni ◽  
Shaun Mahony

AbstractTranscription factor (TF) binding specificity is determined via a complex interplay between the TF’s DNA binding preference and cell type-specific chromatin environments. The chromatin features that correlate with TF binding in a given cell type have been well characterized. For instance, the binding sites for a majority of TFs display concurrent chromatin accessibility. However, concurrent chromatin features reflect the binding activities of the TF itself, and thus provide limited insight into how genome-wide TF-DNA binding patterns became established in the first place. To understand the determinants of TF binding specificity, we therefore need to examine how newly activated TFs interact with sequence and preexisting chromatin landscapes.Here, we investigate the sequence and preexisting chromatin predictors of TF-DNA binding by examining the genome-wide occupancy of TFs that have been induced in well-characterized chromatin environments. We develop Bichrom, a bimodal neural network that jointly models sequence and preexisting chromatin data to interpret the genome-wide binding patterns of induced TFs. We find that the preexisting chromatin landscape is a differential global predictor of TF-DNA binding; incorporating preexisting chromatin features improves our ability to explain the binding specificity of some TFs substantially, but not others. Furthermore, by analyzing site-level predictors, we show that TF binding in previously inaccessible chromatin tends to correspond to the presence of more favorable cognate DNA sequences. Bichrom thus provides a framework for modeling, interpreting, and visualizing the joint sequence and chromatin landscapes that determine TF-DNA binding dynamics.


2021 ◽  
Author(s):  
Kapil Gupta ◽  
Christine Toelzer ◽  
Maia Kavanagh Williamson ◽  
Deborah Shoemark ◽  
A. Sofia F. Oliveira ◽  
...  

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.


2021 ◽  
Author(s):  
David A Gallegos ◽  
Melyssa Minto ◽  
Fang Liu ◽  
Mariah F Hazlett ◽  
S Aryana Yousefzadeh ◽  
...  

Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons. Chromatin accessibility at enhancers predicted cell-type specific gene regulation, identifying transcriptional mechanisms of differential AMPH responses. Finally, we observed dysregulation of multiple PV-specific, AMPH-regulated genes in an Mecp2 mutant mouse strain that shows heightened behavioral sensitivity to psychostimulants, suggesting the functional importance of this transcriptional program. Together these data provide novel insight into the cell-type specific programs of transcriptional plasticity in NAc neurons that underlie addictive-like behaviors.


2019 ◽  
Author(s):  
◽  
Angela Oliveira Pisco ◽  
Aaron McGeever ◽  
Nicholas Schaum ◽  
Jim Karkanias ◽  
...  

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.


2021 ◽  
Author(s):  
John M Rouhana ◽  
Jiali Wang ◽  
Gokcen Eraslan ◽  
Shankara Anand ◽  
Andrew R Hamel ◽  
...  

Summary: ECLIPSER was developed to identify pathogenic cell types and cell type-specific genes that may affect complex disease susceptibility and trait variation by integrating single cell data with known GWAS loci. ECLIPSER maps genes to GWAS loci for a given complex trait based on expression and splicing quantitative trait loci (e/sQTLs) and other functional data, and tests whether the mapped genes are enriched for cell type-specific expression in particular cell types using single-cell/nucleus RNA-seq data from one or more tissues of interest. A Bayesian Fisher's exact test is used to compute fold-enrichment significance. We demonstrate the application of ECLIPSER on various skin diseases and traits using snRNA-seq of healthy human skin samples. Availability and Implementation: The python source code and documentation for ECLIPSER and a Jupyter notebook for generating output tables and figures are available at https://github.com/segrelabgenomics/ECLIPSER. The source code for GWASvar2gene that maps genes to GWAS loci based on e/sQTLs is available at https://github.com/segrelabgenomics/GWASvar2gene. The analysis presented here used data from GTEx (https://gtexportal.org/home/datasets) and Open Targets Genetics (https://genetics-docs.opentargets.org/data-access/graphql-api), but can also be applied to other GWAS variant lists and QTL studies. Data used to reproduce the results of the paper are available in Supplementary data.


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