scholarly journals The hepatocyte clock and feeding control chronophysiology of multiple liver cell types

Science ◽  
2020 ◽  
Vol 369 (6509) ◽  
pp. 1388-1394 ◽  
Author(s):  
Dongyin Guan ◽  
Ying Xiong ◽  
Trang Minh Trinh ◽  
Yang Xiao ◽  
Wenxiang Hu ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
De Novo Lipogenesis ◽  
Diurnal Rhythms ◽  
Molecular Clocks ◽  
Peripheral Clocks ◽  
Multiple Cell ◽  
Feeding Control

Most cells of the body contain molecular clocks, but the requirement of peripheral clocks for rhythmicity and their effects on physiology are not well understood. We show that deletion of core clock components REV-ERBα and REV-ERBβ in adult mouse hepatocytes disrupts diurnal rhythms of a subset of liver genes and alters the diurnal rhythm of de novo lipogenesis. Liver function is also influenced by nonhepatocytic cells, and the loss of hepatocyte REV-ERBs remodels the rhythmic transcriptomes and metabolomes of multiple cell types within the liver. Finally, alteration of food availability demonstrates the hierarchy of the cell-intrinsic hepatocyte clock mechanism and the feeding environment. Together, these studies reveal previously unsuspected roles of the hepatocyte clock in the physiological coordination of nutritional signals and cell-cell communication controlling rhythmic metabolism.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

Exosomes and cardiovascular cell–cell communication

2018 ◽  
Vol 62 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Adam J. Poe ◽  
Anne A. Knowlton
Keyword(s):  
Biological Fluids ◽  
Cell Communication ◽  
Cell Types ◽  
Cardiac Cells ◽  
The Body ◽  
Biologically Active ◽  
Surrounding Tissue ◽  
Intercellular Signaling ◽  
Cardiac Damage ◽  
Almost All

Exosomes have become an important player in intercellular signaling. These lipid microvesicles can stably transfer miRNA, protein, and other molecules between cells and circulate throughout the body. Exosomes are released by almost all cell types and are present in most if not all biological fluids. The biologically active cargo carried by exosomes can alter the phenotype of recipient cells. Exosomes increasingly are recognized as having an important role in the progression and treatment of cardiac disease states. Injured cardiac cells can release exosomes with important pathological effects on surrounding tissue, in addition to effecting other organs. But of equal interest is the possible benefit(s) conferred by exosomes released from stem cells for use in treatment and possible repair of cardiac damage.

scholarly journals Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Xu ◽  
Yu-Qing Ni ◽  
You-Shuo Liu
Keyword(s):  
Cell Communication ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Chronic Inflammatory Disease ◽  
Myocardial Infarctions ◽  
Diagnostic Biomarkers ◽  
Multiple Cell ◽  
Artery Disease ◽  
Intercellular Communications ◽  
Progression Of Atherosclerosis

Atherosclerosis, a complex chronic inflammatory disease, involves multiple alterations of diverse cells, including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), monocytes, macrophages, dendritic cells (DCs), platelets, and even mesenchymal stem cells (MSCs). Globally, it is a common cause of morbidity as well as mortality. It leads to myocardial infarctions, stroke and disabling peripheral artery disease. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that secreted by multiple cell types and play a central role in cell-to-cell communication by delivering various bioactive cargos, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Emerging evidence demonstrated that miRNAs and lncRNAs in EVs are tightly associated with the initiation and development of atherosclerosis. In this review, we will outline and compile the cumulative roles of miRNAs and lncRNAs encapsulated in EVs derived from diverse cells in the progression of atherosclerosis. We also discuss intercellular communications via EVs. In addition, we focused on clinical applications and evaluation of miRNAs and lncRNAs in EVs as potential diagnostic biomarkers and therapeutic targets for atherosclerosis.

scholarly journals ICELLNET: a transcriptome-based framework to dissect intercellular communication

2020 ◽  
Author(s):  
Floriane Noël ◽  
Lucile Massenet-Regad ◽  
Irit Carmi-Levy ◽  
Antonio Cappuccio ◽  
Maximilien Grandclaudon ◽  
...  
Keyword(s):  
Cell Population ◽  
Cell Communication ◽  
Cell Types ◽  
Receptor Expression ◽  
Global Integration ◽  
Cancer Associated Fibroblast ◽  
Receptor Interactions ◽  
Biological Interpretation ◽  
A Cell ◽  
Multiple Cell

AbstractCell-to-cell communication can be inferred from ligand-receptor expression in cell transcriptomic datasets. However, important challenges remain: 1) global integration of cell-to-cell communication, 2) biological interpretation, and 3) application to individual cell population transcriptomic profiles. We developed ICELLNET, a transcriptomic-based framework integrating: 1) an original expert-curated database of ligand-receptor interactions accounting for multiple subunits expression, 2) quantification of communication scores, 3) the possibility to connect a cell population of interest with 31 reference human cell types (BioGPS), and 4) three visualization modes to facilitate biological interpretation. We applied ICELLNET to uncover different communication in breast cancer associated fibroblast (CAF) subsets. ICELLNET also revealed autocrine IL-10 as a switch to control human dendritic cell communication with up to 12 other cell types, four of which were experimentally validated. In summary, ICELLNET is a global, versatile, biologically validated, and easy-to-use framework to dissect cell communication from single or multiple cell-based transcriptomic profile(s).

scholarly journals Two applications of developmental genetics to paleontology: segmentation genes in molluscs and preoral appendages in taxa of uncertain affinity

1992 ◽  
Vol 6 ◽  
pp. 145-145 ◽  
Author(s):  
David K. Jacobs
Keyword(s):  
Fossil Record ◽  
De Novo ◽  
Ectopic Expression ◽  
Cell Types ◽  
The Body ◽  
Developmental Genetics ◽  
Switching Function ◽  
Developmental Sequence ◽  
Homologous Genes ◽  
Organ Systems

Resolution of deep evolutionary problems, including the origin of the metazoa and the morphologic evolution of higher taxa within the metazoa, have long been sought in the developmental sequence. Haeckel's gastraea theory is perhaps the best example of this endeavor. Since Haeckel's time it has become apparent that the early evolution of animal life cannot be read directly from the developmental sequence. Ontogeny itself evolves making it difficult to even identify homologies in the early development between many phyla and classes. However, all may not be lost; during metazoan development gene expression must be localized in order to differentiate cell types in the body during development. It is this regionalized transcription and translation to protein product that differentiates cell types, organ systems, and the morphologic features that we can identify in the fossil record. The functional importance of the genes in question, and the fact that portions of the protein products of these genes must bind to DNA in order to perform their switching function, leads to extreme sequence conservation. This permits the identification and comparison of homologous genes important in the development of divergent taxa even after the passage of the entire Phanerozoic. If these genes retain a pattern of expression in development as well as conservation of the DNA sequence, then we can identify a homologous process derived from the development of the shared ancestor of the two taxa.This approach can be used to address the homology of metameric units. Preliminary results indicate that the segmentation gene engrailed is expressed in chiton trochophores in associated with each of the developing plate fields. The engrailed gene is known to control segmentation processes in arthropods and annelids. Evidently the plates in chitons evolved from serial features in a shared ancestor of annelids, arthropods and molluscs. This indicates that the serial features found in molluscs are ancestral (plesiomorphic), and that the evolution of the mollusca has involved the loss or reduction of serial features rather than their de novo evolution in chitons and monoplacophorans as has been suggested by a number of neontologists. The fossil record suggests successive reduction of serial features in molluscs. This paleontological interpretation now finds support in developmental genetics.Developmental genetics also provides a basis for evolution of body plans. Unusual preoral appendages have evolved in chelicerates, Burgess Shale arthropods such as Yohoia and Leanchoilia, and non arthropod forms such as Opabinia and Tullimonstrum. The differentiation of the vertebral column of vertebrates and the segments of arthropods are controlled by homologous genes that are expressed in a anterior to posterior sequence. Out of place (ectopic) expression of posterior genes in the anterior region produces posterior features in the antennal field of arthropods and in the most anterior vertebrae of the vertebrates. This potential for conversion of anterior features was present in the shared ancestor of vertebrates and arthropods. Thus evolution of novel anterior features resulting from ectopic expression could occur in both deuterostomes and protostomes and may account for a range of novel fossil forms. This suggests that parallel evolution of unusual anterior features could occur, and the presence of these features may not be the best character to use in a phylogenetic analyses.

scholarly journals Predicting cell-to-cell communication networks using NATMI

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rui Hou ◽  
Elena Denisenko ◽  
Huan Ting Ong ◽  
Jordan A. Ramilowski ◽  
Alistair R. R. Forrest
Keyword(s):  
Single Cell ◽  
Communication Networks ◽  
Cell Communication ◽  
Cost Effective ◽  
Cell Types ◽  
Sequencing Technologies ◽  
Multiple Cell ◽  
Multicellular Interactions ◽  
Autocrine Signalling ◽  
Different Cell Types

Abstract Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from diverse samples containing multiple cell types. To study how these different cell types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). NATMI uses connectomeDB2020 (a database of 2293 manually curated ligand-receptor pairs with literature support) to predict and visualise cell-to-cell communication networks from single-cell (or bulk) expression data. Using multiple published single-cell datasets we demonstrate how NATMI can be used to identify (i) the cell-type pairs that are communicating the most (or most specifically) within a network, (ii) the most active (or specific) ligand-receptor pairs active within a network, (iii) putative highly-communicating cellular communities and (iv) differences in intercellular communication when profiling given cell types under different conditions. Furthermore, analysis of the Tabula Muris (organism-wide) atlas confirms our previous prediction that autocrine signalling is a major feature of cell-to-cell communication networks, while also revealing that hundreds of ligands and their cognate receptors are co-expressed in individual cells suggesting a substantial potential for self-signalling.

scholarly journals Notch Signaling in Development, Tissue Homeostasis, and Disease

2017 ◽  
Vol 97 (4) ◽  
pp. 1235-1294 ◽  
Author(s):  
Chris Siebel ◽  
Urban Lendahl
Keyword(s):  
Notch Signaling ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Tissue Homeostasis ◽  
Cell Fates ◽  
Signaling Mechanism ◽  
Transmembrane Receptors ◽  
Notch Gene ◽  
Broad Variety

Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body. In this review, we provide an overview of the Notch signaling mechanism at the molecular level and discuss how the pathway, which is architecturally quite simple, is able to engage in the control of cell fates in a broad variety of cell types. We discuss the current understanding of how Notch signaling can become derailed, either by direct mutations or by aberrant regulation, and the expanding spectrum of diseases and cancers that is a consequence of Notch dysregulation. Finally, we explore the emerging field of Notch in the control of tissue homeostasis, with examples from skin, liver, lung, intestine, and the vasculature.

scholarly journals Healthy lungs maintain a young and energetic body

2021 ◽  
Vol 12 (8) ◽  
pp. 2117-2139
Author(s):  
Florian Ion Tiberiu Petrescu ◽  
Relly Victoria Virgil Petrescu
Keyword(s):  
Cell Types ◽  
The Body ◽  
Pipeline System ◽  
Piping System ◽  
Main Task ◽  
Basal Cells ◽  
Inhaled Particles ◽  
Multiple Cell ◽  
Different Cell Types

In general, life is only possible in the presence of oxygen in a form that can be easily absorbed by the body. In the case of humans, the lungs have as their main task the provision of the oxygen necessary for the body to carry out daily activities. The lung is a paired organ located in the chest cavity, a fibro-elastic organ capable of altering your volume during breathing (inspire and expire). The weight of a lung varies between 800 and 1,000 grams, of which more than 50% is blood. The air reaches the lungs through a pipeline system consisting of Nazo-pharynx, larynx, trachea, bronchi, and bronchiole. The role of the piping system is to heat and dampen the air or to capture and remove foreign inhaled particles. The channel system decreases in diameter after each branch - from the trachea and the large bronchi to the bronchiole with a diameter of less than one millimeter. The lung consists of over 30 different cell types. Trachea and large bronchi are taped by a mucous layer containing multiple cell types: ciliary cells - provides mucus movement, caliciform cells - secretes mucus, basal cells - plays a role in regeneration and neuro-ectodermic cells - ensures the secretory function of the lungs. In the chorion (the deep layer beneath the mucosa) there are cells involved in the defense processes - lymphocytes, mast cells, eosinophils or neutrophils.

scholarly journals Klotho inhibits neuronal senescence in human brain organoids

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mohammed R. Shaker ◽  
Julio Aguado ◽  
Harman Kaur Chaggar ◽  
Ernst J. Wolvetang
Keyword(s):  
Human Brain ◽  
Cortical Neurons ◽  
Brain Aging ◽  
Transmembrane Protein ◽  
Cell Types ◽  
The Body ◽  
Aging Effects ◽  
Multiple Cell ◽  
Senescence Associated Genes

AbstractAging is a major risk factor for many neurodegenerative diseases. Klotho (KL) is a glycosylated transmembrane protein that is expressed in the choroid plexus and neurons of the brain. KL exerts potent anti-aging effects on multiple cell types in the body but its role in human brain cells remains largely unclear. Here we show that human cortical neurons, derived from human pluripotent stem cells in 2D cultures or in cortical organoids, develop the typical hallmarks of senescent cells when maintained in vitro for prolonged periods of time, and that moderate upregulation or repression of endogenous KL expression in cortical organoids inhibits and accelerates senescence, respectively. We further demonstrate that KL expression alters the expression of senescence-associated genes including, extracellular matrix genes, and proteoglycans, and can act in a paracrine fashion to inhibit neuronal senescence. In summary, our results establish an important role for KL in the regulation of human neuronal senescence and offer new mechanistic insight into its role in human brain aging.

scholarly journals Inflammasomes link vascular disease with neuroinflammation and brain disorders

2016 ◽  
Vol 36 (10) ◽  
pp. 1668-1685 ◽  
Author(s):  
Nikolett Lénárt ◽  
David Brough ◽  
Ádám Dénes
Keyword(s):  
Tissue Injury ◽  
Neurological Diseases ◽  
Spatial Scales ◽  
Cell Types ◽  
Cerebrovascular Diseases ◽  
The Body ◽  
Brain Diseases ◽  
Brain Disorders ◽  
Inflammatory Processes ◽  
Multiple Cell

The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer’s or Parkinson’s disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales. However, the mechanisms through which inflammation impacts on neurological disease are improperly defined. To develop effective therapeutic approaches, it is imperative to understand how detrimental inflammatory processes could be blocked selectively, or controlled for prolonged periods, without compromising essential immune defence mechanisms. Increasing evidence indicates that common risk factors for brain disorders, such as atherosclerosis, diabetes, hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4 or AIM2 inflammasomes, which are also associated with various neurological diseases. This review focuses on the mechanisms whereby inflammasomes, which integrate diverse inflammatory signals in response to pathogen-driven stimuli, tissue injury or metabolic alterations in multiple cell types and different organs of the body, could functionally link vascular- and neurological diseases and hence represent a promising therapeutic target.

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