scholarly journals Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

2020 ◽  
Author(s):  
Sang-Hyeop Lee ◽  
Nak-Hyeon Choi ◽  
In-Uk Koh ◽  
Bong-Jo Kim ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Cell Types ◽  
Deposition Process ◽  
Fat Deposition ◽  
Low Grade ◽  
Positive Role ◽  
Inflammatory Genes ◽  
Altered Gene

Abstract BackgroundObesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). ResultsWe defined four classes of differentially expressed genes (DEGs) by comparing gene expression between 1) lean and obese ACs, 2) lean and obese preACs, 3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL6, TNF- and IL-1, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. These two results indicate that (1) up-/downregulation of genes in ACs and preACs is inversely controlled during the fat deposition process and (2) preACs rather than ACs have increased inflammatory response genes in comparisons of lean and obese conditions for each of these cell types. Analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was greater for lean than for obese conditions.ConclusionsTaken together, our analyses may suggest that lean fat differentiation involves even greater enhancement of inflammatory responses than does obese fat differentiation.

scholarly journals Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Sang-Hyeop Lee ◽  
Nak-Hyeon Choi ◽  
In-Uk Koh ◽  
Bong-Jo Kim ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Positive Role ◽  
Inflammatory Genes ◽  
Altered Gene Expression ◽  
Tnf Α ◽  
Altered Gene ◽  
Geo Database

Abstract Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between (1) lean and obese ACs, (2) lean and obese preACs, (3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-α and IL-1β, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

scholarly journals Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

2020 ◽  
Author(s):  
Sang-Hyeop Lee ◽  
Nak-Hyeon Choi ◽  
In-Uk Koh ◽  
Bong-Jo Kim ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Transcriptome Data ◽  
Positive Role ◽  
Inflammatory Genes ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Geo Database

Abstract Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs).Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between 1) lean and obese ACs, 2) lean and obese preACs, 3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-a and IL-1b, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654).Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

scholarly journals Putative Positive Role of Inflammatory Genes in Fat Deposition Supported by Altered Gene Expression in Purified Human Adipocytes and Preadipocytes From Lean and Obese Adipose Tissues

2020 ◽  
Author(s):  
Sang-Hyeop Lee ◽  
Nak-Hyeon Choi ◽  
In-Uk Koh ◽  
Bong-Jo Kim ◽  
Song Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Positive Role ◽  
Inflammatory Genes ◽  
Altered Gene Expression ◽  
Tnf Α ◽  
Altered Gene ◽  
Geo Database

Abstract Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between 1) lean and obese ACs, 2) lean and obese preACs, 3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-α and IL-1β, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. Analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs, because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.

scholarly journals Optimizing expression quantitative trait locus mapping workflows for single-cell studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anna S. E. Cuomo ◽  
Giordano Alvari ◽  
Christina B. Azodi ◽  
Davis J. McCarthy ◽  
Marc Jan Bonder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait Locus ◽  
Single Cell ◽  
Quantitative Trait ◽  
Cell Types ◽  
Expression Quantitative Trait Locus ◽  
Eqtl Mapping ◽  
Trait Locus ◽  
The Impact

Abstract Background Single-cell RNA sequencing (scRNA-seq) has enabled the unbiased, high-throughput quantification of gene expression specific to cell types and states. With the cost of scRNA-seq decreasing and techniques for sample multiplexing improving, population-scale scRNA-seq, and thus single-cell expression quantitative trait locus (sc-eQTL) mapping, is increasingly feasible. Mapping of sc-eQTL provides additional resolution to study the regulatory role of common genetic variants on gene expression across a plethora of cell types and states and promises to improve our understanding of genetic regulation across tissues in both health and disease. Results While previously established methods for bulk eQTL mapping can, in principle, be applied to sc-eQTL mapping, there are a number of open questions about how best to process scRNA-seq data and adapt bulk methods to optimize sc-eQTL mapping. Here, we evaluate the role of different normalization and aggregation strategies, covariate adjustment techniques, and multiple testing correction methods to establish best practice guidelines. We use both real and simulated datasets across single-cell technologies to systematically assess the impact of these different statistical approaches. Conclusion We provide recommendations for future single-cell eQTL studies that can yield up to twice as many eQTL discoveries as default approaches ported from bulk studies.

scholarly journals A single nuclei transcriptomic analysis of the Atlantic salmon gill through smoltification and seawater transfer

2020 ◽  
Author(s):  
Alexander C. West ◽  
Yasutaka Mizoro ◽  
Shona H. Wood ◽  
Louise M. Ince ◽  
Marianne Iversen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atlantic Salmon ◽  
Direct Evidence ◽  
Cell Types ◽  
Prior Work ◽  
In The Wild ◽  
Induced Changes ◽  
Freshwater Environments ◽  
Transcriptomic Studies

AbstractAnadromous salmonids begin life adapted to the freshwater environments of their natal streams before a developmental transition, known as smoltification, transforms them into marine-adapted fish. In the wild, the extending photoperiods of spring stimulates smoltification, typified by radical reprogramming of the gill from an ion-absorbing organ to ion-excreting organ. Prior work has highlighted the role of specialized “mitochondrion-rich” cells in delivering this phenotype. However, transcriptomic studies identify thousands of smoltification-driven differentially regulated genes, indicating that smoltification causes a multifaceted, multicellular change; but direct evidence of this is lacking.Here, we use single-nuclei RNAseq to characterize the Atlantic salmon gill during smoltification and seawater transfer. We identify 20 distinct clusters of nuclei, including known, but also novel gill cell types. These data allow us to isolate cluster-specific, smoltification-induced changes in gene expression. We also show how cellular make-up of the gill changes through smoltification. As expected, we noted an increase in the proportion of seawater mitochondrion-rich cells, however, we also identify a reduction of several immune-related cells. Overall, our results provide unrivaled detail of the cellular complexity in the gill and suggest that smoltification triggers unexpected immune reprogramming directly preceding seawater entry.

scholarly journals Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology

Reproduction ◽  
2011 ◽  
Vol 141 (3) ◽  
pp. 343-355 ◽  
Author(s):  
Michelle L Mujoomdar ◽  
Laura M Hogan ◽  
Albert F Parlow ◽  
Mark W Nachtigal
Keyword(s):  
Gene Expression ◽  
Ovarian Function ◽  
Elevated Serum ◽  
Cell Types ◽  
Reproductive Capacity ◽  
Wide Range ◽  
Altered Gene ◽  
Ovarian Pathology ◽  
Targeted Gene Expression ◽  
Benign Ovarian Tumors

Bioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. ThePcsk6gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6tm1Rob) were obtained, and reproductive parameters (serum hormones, whelping interval, estrus cyclicity, and fertility) were compared toPcsk6+/+mice. WhilePcsk6tm1Robfemale mice are fertile, they manifest reduced reproductive capacity at an accelerated rate relative toPcsk6+/+mice. Reproductive senescence is typically reached by 9 months of age and is correlated with loss of estrus cyclicity, elevated serum FSH levels, and gross alterations in ovarian morphology. A wide range of ovarian morphologies were identified encompassing mild, such as an apparent reduction in follicle number, to moderate – ovarian atrophy with a complete absence of follicles – to severe, manifesting as normal ovarian structures replaced by benign ovarian tumors, including tubulostromal adenomas. Targeted gene expression profiling highlighted changes in RNA expression of molecules involved in processes such as steroidogenesis, gonadotropin signaling, transcriptional regulation, autocrine/paracrine signaling, cholesterol handling, and proprotein bioactivation. These results show that PCSK6 activity plays a role in maintaining normal cellular and tissue homeostasis in the ovary.

Abstract TP99: Human Lung Endothelial Cell Anti-Inflammatory and Regenerative Responses in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Nikunj Satani ◽  
Kaavya Giridhar ◽  
Natalia Wewior ◽  
Dominique D Norris ◽  
Scott D Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Anti Inflammatory ◽  
Lung Endothelial Cells ◽  
Stroke Mimic

Background: Inflammatory responses after stroke consists of central and peripheral immune responses. The role of the spleen after stroke is well-known, however the role of the lungs has not been studied in detail. We explored the relation between stroke severity and immunomodulatory changes in lung endothelial cells. Methods: Human pulmonary endothelial cells (hPECs, Cell Biologics) were cultured at passage 3. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 20 was collected at 24 hours after stroke. hPECs were exposed to media with 1) 10% FBS alone (N=6), 2) 10% serum from stroke patients (N=72), or 3) 10% serum from stroke mimic patients (N=6). After 3 hour of exposure, fresh media was added and secretomes from hPECs were measured after 24 hours. We isolated RNA from hPECs after 3 hour of serum exposure and measured gene expression (N=6 for each group). Secretome and gene changes in hPECs were analyzed based on stroke severity, tPA treatment, and co-morbidities. Results: Serum from stroke patients reduced the secretion of IL-8, MCP-1 and Fractalkine (p<0.01), and increased the secretion of VEGF and BDNF (p<0.01) from hPECs. These effects were more pronounced depending on stroke severity (Fig). There was no effect of tPA or T2DM on hPECs secretomes. There was significantly reduced gene expression of IL-6, IL-8, MCP-1 and IL-1β and significantly higher expression of ICAM1, IGF-1 and TGF-β1 as compared to stroke mimics. Conclusion: Exposure of hPECs to serum from stroke patients alters their immunomodulatory properties. Higher severity of stroke leads to more protective response from hPECs by reducing the secretion of pro-inflammatory factors, while increasing the secretion of anti-inflammatory factors.

Untraditional methods for targeting the kidney in transgenic mice

2003 ◽  
Vol 285 (6) ◽  
pp. F1027-F1033 ◽  
Author(s):  
Robert A. Bianco ◽  
Henry L. Keen ◽  
Julie L. Lavoie ◽  
Curt D. Sigmund
Keyword(s):  
Gene Expression ◽  
Human Genome Project ◽  
Target Gene ◽  
Cell Types ◽  
Experimental Models ◽  
Genome Project ◽  
Renal Physiology ◽  
Physiological Relevance ◽  
The Human Genome Project

With the completion of the human genome project and the sequencing of many genomes of experimental models, there is a pressing need to determine the physiological relevance of newly identified genes. Gene-targeting approaches have become an important tool in our arsenal to dissect the significance of genes expressed in many tissues. A wealth of experimental models has been made to assess the role of gene expression in renal function and development. The development of new and informative models is presently limited by the anatomic complexity of the kidney and the lack of cell-specific promoters to target the numerous diverse cell types in that organ. Because of this, new approaches may have to be developed. In this review, we will discuss several untraditional methods to target gene expression to the kidney. These approaches should provide some additional tricks and tools to help in developing additional informative models for studying renal physiology.

scholarly journals Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 19 ◽  
Author(s):  
Harmen Hawer ◽  
Alexander Hammermeister ◽  
Keerthiraju Ravichandran ◽  
Sebastian Glatt ◽  
Raffael Schaffrath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Disease ◽  
Messenger Rna ◽  
Environmental Changes ◽  
Mrna Translation ◽  
Regulatory Control ◽  
Trna Modification ◽  
Positive Role ◽  
Trna Modifications

Transfer RNA (tRNA) is subject to a multitude of posttranscriptional modifications which can profoundly impact its functionality as the essential adaptor molecule in messenger RNA (mRNA) translation. Therefore, dynamic regulation of tRNA modification in response to environmental changes can tune the efficiency of gene expression in concert with the emerging epitranscriptomic mRNA regulators. Several of the tRNA modifications are required to prevent human diseases and are particularly important for proper development and generation of neurons. In addition to the positive role of different tRNA modifications in prevention of neurodegeneration, certain cancer types upregulate tRNA modification genes to sustain cancer cell gene expression and metastasis. Multiple associations of defects in genes encoding subunits of the tRNA modifier complex Elongator with human disease highlight the importance of proper anticodon wobble uridine modifications (xm5U34) for health. Elongator functionality requires communication with accessory proteins and dynamic phosphorylation, providing regulatory control of its function. Here, we summarized recent insights into molecular functions of the complex and the role of Elongator dependent tRNA modification in human disease.

scholarly journals Adrenergic Regulation of Macrophage-Mediated Innate/Inflammatory Responses in Obesity and Exercise in this Condition: Role of β2 Adrenergic Receptors

2019 ◽  
Vol 19 (8) ◽  
pp. 1089-1099 ◽  
Author(s):  
Eduardo Ortega ◽  
Isabel Gálvez ◽  
Leticia Martín-Cordero
Keyword(s):  
Stress Responses ◽  
Adrenergic Receptors ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Adrenergic Stimulation ◽  
Adrenergic Regulation ◽  
Induce Insulin Resistance ◽  
Antiinflammatory Effects ◽  
Β Adrenergic Receptors

Background: The effects of exercise on the innate/inflammatory immune responses are crucially mediated by catecholamines and adrenoreceptors; and mediations in both stimulatory and anti-inflammatory responses have been attributed to them. Obesity and metabolic syndrome are included among low-grade chronic inflammatory pathologies; particularly because patients have a dysregulation of the inflammatory and stress responses, which can lead to high levels of inflammatory cytokines that induce insulin resistance, contributing to the onset or exacerbation of type 2 diabetes. Macrophages play a crucial role in this obesity-induced inflammation. Although most of the antiinflammatory effects of catecholamines are mediated by β adrenergic receptors (particularly β2), it is not known whether in altered homeostatic conditions, such as obesity and during exercise, innate/ inflammatory responses of macrophages to β2 adrenergic stimulation are similar to those in cells of healthy organisms at baseline. Objective: This review aims to emphasize that there could be possible different responses to β2 adrenergic stimulation in obesity, and exercise in this condition. Methods: A revision of the literature based on the hypothesis that obesity affects β2 adrenergic regulation of macrophage-mediated innate/inflammatory responses, as well as the effect of exercise in this context. Conclusion: The inflammatory responses mediated by β2 adrenoreceptors are different in obese individuals with altered inflammatory states at baseline compared to healthy individuals, and exercise can also interfere with these responses. Nevertheless, it is clearly necessary to develop more studies that contribute to widening the knowledge of the neuroimmune regulation process in obesity, particularly in this context.

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