Role of Different Sponge Cell Types in Species Specific Cell Aggregation

Tumor microenvironment (TME) formation is a major cause of immunosuppression. The TME consists of a considerable number of macrophages and stromal cells that have been identified in multiple tumor types. CCL2 is the strongest chemoattractant involved in macrophage recruitment and a powerful initiator of inflammation. Evidence indicates that CCL2 can attract other host cells in the TME and direct their differentiation in cooperation with other cytokines. Overall, CCL2 has an unfavorable effect on prognosis in tumor patients because of the accumulation of immunosuppressive cell subtypes. However, there is also evidence demonstrating that CCL2 enhances the anti-tumor capability of specific cell types such as inflammatory monocytes and neutrophils. The inflammation state of the tumor seems to have a bi-lateral role in tumor progression. Here, we review works focusing on the interactions between cancer cells and host cells, and on the biological role of CCL2 in these processes.

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Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways

10.1101/214973 ◽

2018 ◽

Cited By ~ 13

Author(s):

Philip R. Jansen ◽

Kyoko Watanabe ◽

Sven Stringer ◽

Nathan Skene ◽

Julien Bryois ◽

...

Keyword(s):

Animal Studies ◽

Genetic Correlations ◽

Cell Types ◽

Reward Processing ◽

Chromatin Interaction ◽

Specific Cell ◽

Metabolic Traits ◽

Genome Wide ◽

Insight Into

AbstractInsomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia complaints. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.

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Rescue of Hepatic Phospholipid Remodeling Defect in iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver

Biomolecules ◽

10.3390/biom10091332 ◽

2020 ◽

Vol 10 (9) ◽

pp. 1332

Author(s):

Walee Chamulitrat ◽

Chutima Jansakun ◽

Huili Li ◽

Gerhard Liebisch

Keyword(s):

Fatty Liver ◽

Cell Types ◽

Specific Cell ◽

Liver Inflammation ◽

Alcoholic Fatty Liver ◽

Calcium Independent Phospholipase A2 ◽

Hydrolysis Of

Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β or PLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. The ubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fatty acid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liver disease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mouse models; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) as well as feeding with methionine- and choline-deficient (MCD) diet (representing non-obese NAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acids and a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLD models. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models. iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD » MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was even exaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observed in iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2β deletion in specific cell types such as macrophages may render liver inflammation and fibrosis, independent of steatosis protection.

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Developmental regulation and tissue distribution of the liver transcription factor LFB1 (HNF1) in Xenopus laevis.

Molecular and Cellular Biology ◽

10.1128/mcb.13.1.421 ◽

1993 ◽

Vol 13 (1) ◽

pp. 421-431 ◽

Cited By ~ 28

Author(s):

S Bartkowski ◽

D Zapp ◽

H Weber ◽

G Eberle ◽

C Zoidl ◽

...

Keyword(s):

Transcription Factor ◽

Xenopus Laevis ◽

Developmental Regulation ◽

Cdna Probe ◽

Cell Types ◽

Specific Gene ◽

Specific Cell ◽

Early Appearance ◽

Liver Cdna Library

The transcription factor LFB1 (HNF1) was initially identified as a regulator of liver-specific gene expression in mammals. It interacts with the promoter element HP1, which is functionally conserved between mammals and amphibians, suggesting that a homologous factor, XLFB1, also exists in Xenopus laevis. To study the role of LFB1 in early development, we isolated two groups of cDNAs coding for this factor from a Xenopus liver cDNA library by using a rat LFB1 cDNA probe. A comparison of the primary structures of the Xenopus and mammalian proteins shows that the myosin-like dimerization helix, the POU-A-related domain, the homeo-domain-related region, and the serine/threonine-rich activation domain are conserved between X. laevis and mammals, suggesting that all these features typical for LFB1 are essential for function. Using monoclonal antibodies, we demonstrate that XLFB1 is present not only in the liver but also in the stomach, intestine, colon, and kidney. In an analysis of the expression of XLFB1 in the developing Xenopus embryo, XLFB1 transcripts appear at the gastrula stage. The XLFB1 protein can be identified in regions of the embryo in which the liver diverticulum, stomach, gut, and pronephros are localized. The early appearance of XLFB1 expression during embryogenesis suggests that the tissue-specific transcription factor XLFB1 is involved in the determination and/or differentiation of specific cell types during organogenesis.

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Cell-autonomous expression of the acid hydrolase galactocerebrosidase

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1917675117 ◽

2020 ◽

Vol 117 (16) ◽

pp. 9032-9041

Author(s):

Christina R. Mikulka ◽

Joshua T. Dearborn ◽

Bruno A. Benitez ◽

Amy Strickland ◽

Lin Liu ◽

...

Keyword(s):

Lysosomal Storage Diseases ◽

Cell Types ◽

Krabbe Disease ◽

Specific Cell ◽

Acid Hydrolase ◽

Lysosomal Storage ◽

Lysosomal Hydrolases ◽

Soluble Acid ◽

Enzyme Deficient

Lysosomal storage diseases (LSDs) are typically caused by a deficiency in a soluble acid hydrolase and are characterized by the accumulation of undegraded substrates in the lysosome. Determining the role of specific cell types in the pathogenesis of LSDs is a major challenge due to the secretion and subsequent uptake of lysosomal hydrolases by adjacent cells, often referred to as “cross-correction.” Here we create and validate a conditional mouse model for cell-autonomous expression of galactocerebrosidase (GALC), the lysosomal enzyme deficient in Krabbe disease. We show that lysosomal membrane-tethered GALC (GALCLAMP1) retains enzyme activity, is able to cleave galactosylsphingosine, and is unable to cross-correct. Ubiquitous expression of GALCLAMP1 fully rescues the phenotype of the GALC-deficient mouse (Twitcher), and widespread deletion of GALCLAMP1 recapitulates the Twitcher phenotype. We demonstrate the utility of this model by deleting GALCLAMP1 specifically in myelinating Schwann cells in order to characterize the peripheral neuropathy seen in Krabbe disease.

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Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

International Journal of Molecular Sciences ◽

10.3390/ijms22062870 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2870

Author(s):

Tsung-Chieh Lin ◽

Michael Hsiao

Keyword(s):

Cancer Progression ◽

Molecular Mechanisms ◽

Leptin Receptor ◽

Biological Effects ◽

Prognostic Significance ◽

Cell Types ◽

Receptor Expression ◽

Specific Cell ◽

Signaling Axis

Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

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Dynamic Role of Phospholipases A2 in Health and Diseases in the Central Nervous System

Cells ◽

10.3390/cells10112963 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2963

Author(s):

Grace Y. Sun ◽

Xue Geng ◽

Tao Teng ◽

Bo Yang ◽

Michael K. Appenteng ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cellular Localization ◽

Cell Types ◽

Molecular Structures ◽

Specific Cell ◽

Phospholipases A2 ◽

Cell Functions ◽

The Central Nervous System

Phospholipids are major components in the lipid bilayer of cell membranes. These molecules are comprised of two acyl or alkyl groups and different phospho-base groups linked to the glycerol backbone. Over the years, substantial interest has focused on metabolism of phospholipids by phospholipases and the role of their metabolic products in mediating cell functions. The high levels of polyunsaturated fatty acids (PUFA) in the central nervous system (CNS) have led to studies centered on phospholipases A2 (PLA2s), enzymes responsible for cleaving the acyl groups at the sn-2 position of the phospholipids and resulting in production of PUFA and lysophospholipids. Among the many subtypes of PLA2s, studies have centered on three major types of PLA2s, namely, the calcium-dependent cytosolic cPLA2, the calcium-independent iPLA2 and the secretory sPLA2. These PLA2s are different in their molecular structures, cellular localization and, thus, production of lipid mediators with diverse functions. In the past, studies on specific role of PLA2 on cells in the CNS are limited, partly because of the complex cellular make-up of the nervous tissue. However, understanding of the molecular actions of these PLA2s have improved with recent advances in techniques for separation and isolation of specific cell types in the brain tissue as well as development of sensitive molecular tools for analyses of proteins and lipids. A major goal here is to summarize recent studies on the characteristics and dynamic roles of the three major types of PLA2s and their oxidative products towards brain health and neurological disorders.

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Expansin-controlled cell wall stiffness regulates root growth in Arabidopsis

10.1101/2020.06.25.170969 ◽

2020 ◽

Author(s):

Marketa Samalova ◽

Kareem Elsayad ◽

Alesia Melnikava ◽

Alexis Peaucelle ◽

Evelina Gahurova ◽

...

Keyword(s):

Cell Wall ◽

Root Growth ◽

Cell Types ◽

Root Apical Meristem ◽

Specific Cell ◽

Wall Stiffness ◽

Specific Localization ◽

Dependent Cell ◽

Cell Type Specific

ABSTRACTExpansins facilitate cell expansion via mediating pH-dependent cell wall (CW) loosening. However, the role of expansins in the control of biomechanical CW properties in the tissue and organ context remains elusive. We determined hormonal responsiveness and specificity of expression and localization of expansins predicted to be direct targets of cytokinin signalling. We found EXPA1 homogenously distributed throughout the CW of columella/ lateral root cap, while EXPA10 and EXPA14 localized predominantly at the three-cell boundaries of epidermis/cortex in various root zones. Cell type-specific localization of EXPA15 overlaps with higher CW stiffness measured via Brillouin light scattering microscopy. As indicated by both Brillouin frequency shift and AFM-measured Young’s modulus, EXPA1 overexpression upregulated CW stiffness, associated with shortening of the root apical meristem and root growth arrest. We propose that root growth in Arabidopsis requires delicate orchestration of biomechanical CW properties via tight regulation of various expansins’ localization to specific cell types and extracellular domains.

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The Endocannabinoid System in Glial Cells and Their Profitable Interactions to Treat Epilepsy: Evidence from Animal Models

International Journal of Molecular Sciences ◽

10.3390/ijms222413231 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13231

Author(s):

Jon Egaña-Huguet ◽

Edgar Soria-Gómez ◽

Pedro Grandes

Keyword(s):

Glial Cells ◽

Endocannabinoid System ◽

Cell Types ◽

Specific Cell ◽

Neuronal Viability ◽

Wide Range ◽

Novel Target ◽

Different Cell Types ◽

The Impact

Epilepsy is one of the most common neurological conditions. Yearly, five million people are diagnosed with epileptic-related disorders. The neuroprotective and therapeutic effect of (endo)cannabinoid compounds has been extensively investigated in several models of epilepsy. Therefore, the study of specific cell-type-dependent mechanisms underlying cannabinoid effects is crucial to understanding epileptic disorders. It is estimated that about 100 billion neurons and a roughly equal number of glial cells co-exist in the human brain. The glial population is in charge of neuronal viability, and therefore, their participation in brain pathophysiology is crucial. Furthermore, glial malfunctioning occurs in a wide range of neurological disorders. However, little is known about the impact of the endocannabinoid system (ECS) regulation over glial cells, even less in pathological conditions such as epilepsy. In this review, we aim to compile the existing knowledge on the role of the ECS in different cell types, with a particular emphasis on glial cells and their impact on epilepsy. Thus, we propose that glial cells could be a novel target for cannabinoid agents for treating the etiology of epilepsy and managing seizure-like disorders.

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