Developmental and Functional Heterogeneity of White Adipocytes within a Single Fat Depot
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PROVIDER: PRJNA433939 | ENA |
REPOSITORIES: ENA
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Project description:We and others have previously observed that adipocytes and preadipocytes taken from different adipose tissue depots are characterized by differential expression of developmental and patterning genes (Dankel et al., 2010; Ferrer-Lorente et al., 2014; Gesta et al., 2006; Lee et al., 2017a; Lee et al., 2013; Macotela et al., 2012; Tchkonia et al., 2007; Yamamoto et al., 2010). To investigate how adipocyte heterogeneity and differences in the expression of developmental genes might impact the biology of adipocytes and preadipocytes, we created preadipocyte cell lines from the stromovascular fraction (SVF) isolated from the scapular white, inguinal, perigonadal, perirenal, and mesenteric fat pads of 6-week old male Immortomouse™ (Jat et al., 1991).During routine culture of the subcutaneous and visceral/perigonadal clonal cell lines, we observed extreme variation in media acidification rates that was unrelated to the fat pad of origin, the differentiation capacity of the cells, or the rate of their proliferation, suggesting metabolic heterogeneity. To further investigate this possibility, 24 clonal cell lines (12 each from subcutaneous and perigonadal fat) were selected based on variable media acidification rates, and their mRNA expression pattern determined by microarray analysis. The expression data was clustered using three different algorythms, and the consensus was used to categorize each type of adipose tissue.
2019-02-01 | GSE110531 | GEO
Project description:Recent studies suggest that, even within a single adipose depot, there may be distinct subpopulations of adipocytes. To investigate this cellular heterogeneity, we have developed multiple conditionally immortalized clonal preadipocyte lines from white adipose tissue of mice. Analysis of these clones reveals at least three white adipocyte subpopulations. These subpopulations have differences in metabolism and differentially respond to inflammatory cytokines, insulin, and growth hormones. These also have distinct gene expression profiles and can be tracked by differential expression of three marker genes: Wilms' tumor 1, transgelin, and myxovirus 1. Lineage tracing analysis with dual-fluorescent reporter mice indicates that these adipocyte subpopulations have differences in gene expression and metabolism that mirror those observed in the clonal cell lines. Furthermore, preadipocytes and adipocytes from these subpopulations differ in their abundance in different fat depots. Thus, white adipose tissue, even in a single depot, is comprised of distinct subpopulations of white adipocytes with different physiological phenotypes. These differences in adipocyte composition may contribute to the differences in metabolic behavior and physiology of different fat depots.
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Project description:Visceral adiposity is a risk factor for severe COVID-19 and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 undergoes productive infection in adipocytes, although the degree of infection and the cellular response depend on the anatomical origin of the adipocyte and the viral strain. Differentiated adipocytes from human visceral adipose tissue are more permissive to SARS-CoV-2 infection than their subcutaneous counterpart, and this associates with ACE2 expression. Infection of subcutaneous adipocytes leads to inhibition of lipolysis, while infection of visceral adipocytes results in higher expression of pro-inflammatory cytokines. Infected adipocytes begin to die 4 days after infection, regardless of the origin. The viral load and cellular response are attenuated when adipocytes are infected with the SARS-CoV-2 variant P.1. Hence, SARS-CoV-2 infects and replicates in adipocytes, where it compromises cell viability and alters lipid metabolism or elicits a pro-inflammatory response depending on the fat depot and the viral strain.
2024-02-29 | PXD030910 | Pride
Project description:Here we have employed chromatin immunoprecipitation combined with deep sequencing to map and compare PPARM-NM-3 binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPARM-NM-3 binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARM-NM-3 binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARM-NM-3 binding sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARM-NM-3 is associated with highly depot-specific gene expression. This indicates that PPARM-NM-3 plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARM-NM-3 lineage-specific recruitment even when differentiated in vitro. Examination of PPARM-NM-3 binding in in vitro differentiatied adipocytes isolated from three different adipose depots.
2012-10-11 | E-GEOD-41481 | biostudies-arrayexpress
Project description:Here we have employed chromatin immunoprecipitation combined with deep sequencing to map and compare PPARγ binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPARγ binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARγ binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARγ binding sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARγ is associated with highly depot-specific gene expression. This indicates that PPARγ plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARγ lineage-specific recruitment even when differentiated in vitro.
2012-10-11 | GSE41481 | GEO
Project description:Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA-sequencing (snRNA-seq) analyses largely uncovered overlapping/similar cell-type landscapes. We hypothesized that adipocytes subtypes, differentiation trajectories, and/or intercellular communication patterns could illuminate this depot similarity-difference gap. For this, we performed snRNA-seq of human subcutaneous/visceral adipose tissues (5/10 samples, respectively). Of 27,665 adipocyte nuclei in both depots, the majority were “classical”, namely- enriched in lipid metabolism pathways. However, we also observed “non-classical” adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization/angiogenesis, or ribosomal processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via non-classical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Lastly, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation, and intercellular communication patterns to human fat depot differences.
2024-11-11 | GSE281356 | GEO
Project description:White adipose tissue (WAT) requires extracellular Ca2+ influx for lipolysis, differentiation, and expansion. This partly occurs via plasma membrane Ca2+ voltage-dependent channels (CaVs). However, WFA exists in different depots whose function varies with age, sex, and location. To explore whether their CaV expression profiles also differ we used RNAseq and qPCR on gonadal, mesenteric, retroperitoneal, and inguinal subcutaneous fat depots from rats of different ages and sex. CaV expression was found dependent on age, sex, and WFA location. In the gonadal depots of both sexes a significantly lower expression of CaV1.2 and CaV1.3 was seen for adults compared to pre-pubescent juveniles. A lower level of expression was also seen for CaV3.1 in adult male but not female gonadal WFA, the latter of whose expression remained unchanged with age. Relatively little expression of CaV3.2 and 3.2 was observed. In post-pubescent inguinal subcutaneous fat, where the third and fourth mammary glands are located, CaV3.1 was decreased in males but increased in females - thus suggesting that this channel is associated with mammogenesis; however, no difference in intracellular Ca2+ levels or adipocyte size were noted. For all adult depots, CaV3.1 expression was larger in females than males - a difference not seen in pre-pubescent rats. These observations are consistent with the changes of CaV3.1 expression seen in 3T3-L1 cell differentiation and the ability of selective CaV3.1 antagonists to inhibit adipogensis. Our results show that changes in CaV expression patterns occur in fat depots related to sexual dimorphism: reproductive tracts and mammogenesis.
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Project description:Case story. A patient with massive infiltration of the visceral adipose tissue depot by BAT in a patient with a catecholamine secreting paraganglioma. BAT tissue was identified by protein expression of UCP1 (western blotting and immunostaining) The goal of the study is to identify patterns of gene expression in BAT containing visceral fat compared to the patient's own subcutanous fat which did not express BAT. For comparison a pool of mRNA isolated from visceral fat from obese subjects was used. Patient Case, Gene expression array from a biopsy from the patient's visceral fat and a biopsy from the subcutaneous fat compared to one array of mRNA from the visceral depot pooled from a group of obese subjects
2014-08-12 | E-GEOD-49795 | biostudies-arrayexpress
Project description:The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.
2024-09-10 | GSE242977 | GEO
Project description:Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female sheep. Adipocytes are key regulators of insulin sensitivity and tissue-specific differences in insulin sensitivity, coupled with adipose depot-specific changes in key mRNAs, were previously observed. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) regulators of gene expression would prevail to account for the direction of changes seen in mRNAs. Noncoding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific that were mutually exclusive suggestive of different regulatory entry points in this regulation.
2024-04-21 | GSE219111 | GEO