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Kerrin S Small - One of the best experts on this subject based on the ideXlab platform.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
American Journal of Human Genetics, 2019Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is an important endocrine organ with a role in many cardiometabolic diseases. It is comprised of a heterogeneous collection of Cell types that can differentially impact disease phenotypes. Cellular heterogeneity can also confound -omic analyses but is rarely taken into account in analysis of solid-Tissue transcriptomes. Here, we investigate Cell-type heterogeneity in two population-level subcutaneous Adipose-Tissue RNA-seq datasets (TwinsUK, n = 766 and the Genotype-Tissue Expression project [GTEx], n = 326) by estimating the relative proportions of four distinct Cell types (adipocytes, macrophages, CD4+ T Cells, and micro-vascular endothelial Cells). We find significant Cellular heterogeneity within and between the TwinsUK and GTEx Adipose datasets. We find that Adipose Cell-type composition is heritable and confirm the positive association between Adipose-resident macrophage proportion and obesity (high BMI), but we find a stronger BMI-independent association with dual-energy X-ray absorptiometry (DXA) derived body-fat distribution traits. We benchmark the impact of Adipose-Tissue Cell composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks, and cis-eQTL discovery. Our results indicate that it is critical to account for Cell-type composition when combining Adipose transcriptome datasets in co-expression analysis and in differential expression analysis with obesity-related traits. We applied gene expression by Cell-type proportion interaction models (G × Cell) to identify 26 Cell-type-specific expression quantitative trait loci (eQTLs) in 20 genes, including four autoimmune disease genome-wide association study (GWAS) loci. These results identify Cell-specific eQTLs and demonstrate the potential of in silico deconvolution of bulk Tissue to identify Cell-type-restricted regulatory variants.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
bioRxiv, 2018Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is comprised of a heterogeneous collection of Cell-types which can differentially impact disease phenotypes. We investigated Cell-type heterogeneity in two population-level subcutaneous Adipose Tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that Adipose Cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound omic analyses, but is rarely taken into account in analysis of solid-Tissue transcriptomes. We benchmark the impact of Adipose Tissue Cell-composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 Cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk Tissue to identify Cell-type restricted regulatory variants.
Craig A Glastonbury - One of the best experts on this subject based on the ideXlab platform.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
American Journal of Human Genetics, 2019Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is an important endocrine organ with a role in many cardiometabolic diseases. It is comprised of a heterogeneous collection of Cell types that can differentially impact disease phenotypes. Cellular heterogeneity can also confound -omic analyses but is rarely taken into account in analysis of solid-Tissue transcriptomes. Here, we investigate Cell-type heterogeneity in two population-level subcutaneous Adipose-Tissue RNA-seq datasets (TwinsUK, n = 766 and the Genotype-Tissue Expression project [GTEx], n = 326) by estimating the relative proportions of four distinct Cell types (adipocytes, macrophages, CD4+ T Cells, and micro-vascular endothelial Cells). We find significant Cellular heterogeneity within and between the TwinsUK and GTEx Adipose datasets. We find that Adipose Cell-type composition is heritable and confirm the positive association between Adipose-resident macrophage proportion and obesity (high BMI), but we find a stronger BMI-independent association with dual-energy X-ray absorptiometry (DXA) derived body-fat distribution traits. We benchmark the impact of Adipose-Tissue Cell composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks, and cis-eQTL discovery. Our results indicate that it is critical to account for Cell-type composition when combining Adipose transcriptome datasets in co-expression analysis and in differential expression analysis with obesity-related traits. We applied gene expression by Cell-type proportion interaction models (G × Cell) to identify 26 Cell-type-specific expression quantitative trait loci (eQTLs) in 20 genes, including four autoimmune disease genome-wide association study (GWAS) loci. These results identify Cell-specific eQTLs and demonstrate the potential of in silico deconvolution of bulk Tissue to identify Cell-type-restricted regulatory variants.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
bioRxiv, 2018Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is comprised of a heterogeneous collection of Cell-types which can differentially impact disease phenotypes. We investigated Cell-type heterogeneity in two population-level subcutaneous Adipose Tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that Adipose Cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound omic analyses, but is rarely taken into account in analysis of solid-Tissue transcriptomes. We benchmark the impact of Adipose Tissue Cell-composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 Cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk Tissue to identify Cell-type restricted regulatory variants.
Julia Elsayed S Moustafa - One of the best experts on this subject based on the ideXlab platform.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
American Journal of Human Genetics, 2019Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is an important endocrine organ with a role in many cardiometabolic diseases. It is comprised of a heterogeneous collection of Cell types that can differentially impact disease phenotypes. Cellular heterogeneity can also confound -omic analyses but is rarely taken into account in analysis of solid-Tissue transcriptomes. Here, we investigate Cell-type heterogeneity in two population-level subcutaneous Adipose-Tissue RNA-seq datasets (TwinsUK, n = 766 and the Genotype-Tissue Expression project [GTEx], n = 326) by estimating the relative proportions of four distinct Cell types (adipocytes, macrophages, CD4+ T Cells, and micro-vascular endothelial Cells). We find significant Cellular heterogeneity within and between the TwinsUK and GTEx Adipose datasets. We find that Adipose Cell-type composition is heritable and confirm the positive association between Adipose-resident macrophage proportion and obesity (high BMI), but we find a stronger BMI-independent association with dual-energy X-ray absorptiometry (DXA) derived body-fat distribution traits. We benchmark the impact of Adipose-Tissue Cell composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks, and cis-eQTL discovery. Our results indicate that it is critical to account for Cell-type composition when combining Adipose transcriptome datasets in co-expression analysis and in differential expression analysis with obesity-related traits. We applied gene expression by Cell-type proportion interaction models (G × Cell) to identify 26 Cell-type-specific expression quantitative trait loci (eQTLs) in 20 genes, including four autoimmune disease genome-wide association study (GWAS) loci. These results identify Cell-specific eQTLs and demonstrate the potential of in silico deconvolution of bulk Tissue to identify Cell-type-restricted regulatory variants.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
bioRxiv, 2018Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is comprised of a heterogeneous collection of Cell-types which can differentially impact disease phenotypes. We investigated Cell-type heterogeneity in two population-level subcutaneous Adipose Tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that Adipose Cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound omic analyses, but is rarely taken into account in analysis of solid-Tissue transcriptomes. We benchmark the impact of Adipose Tissue Cell-composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 Cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk Tissue to identify Cell-type restricted regulatory variants.
Alexessander Couto Alves - One of the best experts on this subject based on the ideXlab platform.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
American Journal of Human Genetics, 2019Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is an important endocrine organ with a role in many cardiometabolic diseases. It is comprised of a heterogeneous collection of Cell types that can differentially impact disease phenotypes. Cellular heterogeneity can also confound -omic analyses but is rarely taken into account in analysis of solid-Tissue transcriptomes. Here, we investigate Cell-type heterogeneity in two population-level subcutaneous Adipose-Tissue RNA-seq datasets (TwinsUK, n = 766 and the Genotype-Tissue Expression project [GTEx], n = 326) by estimating the relative proportions of four distinct Cell types (adipocytes, macrophages, CD4+ T Cells, and micro-vascular endothelial Cells). We find significant Cellular heterogeneity within and between the TwinsUK and GTEx Adipose datasets. We find that Adipose Cell-type composition is heritable and confirm the positive association between Adipose-resident macrophage proportion and obesity (high BMI), but we find a stronger BMI-independent association with dual-energy X-ray absorptiometry (DXA) derived body-fat distribution traits. We benchmark the impact of Adipose-Tissue Cell composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks, and cis-eQTL discovery. Our results indicate that it is critical to account for Cell-type composition when combining Adipose transcriptome datasets in co-expression analysis and in differential expression analysis with obesity-related traits. We applied gene expression by Cell-type proportion interaction models (G × Cell) to identify 26 Cell-type-specific expression quantitative trait loci (eQTLs) in 20 genes, including four autoimmune disease genome-wide association study (GWAS) loci. These results identify Cell-specific eQTLs and demonstrate the potential of in silico deconvolution of bulk Tissue to identify Cell-type-restricted regulatory variants.
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Cell type heterogeneity in Adipose Tissue is associated with complex traits and reveals disease relevant Cell specific eqtls
bioRxiv, 2018Co-Authors: Craig A Glastonbury, Alexessander Couto Alves, Julia Elsayed S Moustafa, Kerrin S SmallAbstract:Adipose Tissue is comprised of a heterogeneous collection of Cell-types which can differentially impact disease phenotypes. We investigated Cell-type heterogeneity in two population-level subcutaneous Adipose Tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that Adipose Cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound omic analyses, but is rarely taken into account in analysis of solid-Tissue transcriptomes. We benchmark the impact of Adipose Tissue Cell-composition on a range of standard analyses, including phenotype-gene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 Cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk Tissue to identify Cell-type restricted regulatory variants.
Marià Alemany - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of rat Adipose Tissue Cell recovery, and non-fat Cell volume, in primary Cell cultures
PeerJ, 2016Co-Authors: Floriana Rotondo, María Del Mar Romero, Ana Cecilia Ho-palma, Xavier Remesar, José Antonio Fernández-lópez, Marià AlemanyAbstract:Dades primaries associades a un article publicat a la revista PeerJ disponible a l'adreca http://dx.doi.org/10.7717/peerj.2725
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Quantitative analysis of rat Adipose Tissue Cell recovery, and non-fat Cell volume, in primary Cell cultures
2016Co-Authors: Floriana Rotondo, Ana Cecilia Ho-palma, Xavier Remesar, José Antonio Fernández-lópez, María Del Mar Romero, Marià AlemanyAbstract:Background. White Adipose Tissue (WAT) is a complex, disperse, multifunctional organ which contains adipocytes, and a large proportion of fat, but also other Cell types, active in defence, regeneration and signalling functions. Studies with adipocytes often require their isolation from WAT breaking up the matrix collagen fibres, but primary cultures of these Cells could not be easily correlated to intact WAT, since often recovery and viability are unknown. Experimental design. Epididymal WAT of 4-6 young adult rats was used to isolate adipocytes with collagenase. Careful recording of lipid content of Tissue, and all fraction volumes and weights, allowed us to trace the amount of initial WAT fat remaining in the Cell preparation. Functionality was estimated by incubation with glucose and measurement of lactate production. Non-adipocyte Cells were also recovered and their sizes (and those of adipocytes) were also measured. The presence of non-nucleated Cells (erythrocytes) was also estimated. Results. Cell numbers and sizes were correlated from all fractions to intact WAT. Tracing the lipid content, the recovery of adipocytes in the final, metabolically active, preparation was in the range of 70-75%. Adipocytes were 7%, erythrocytes 68% and other stromal (nucleated Cells) 24% of total WAT Cells. However, their overall volumes were, 91%, 0.05%, and 0.2% of WAT. Non-fat volume of adipocytes was 2.5% of WAT. Conclusions. The methodology presented here allows for a direct quantitative reference to the original Tissue of studies using isolated Cells. We have found, also, that the "live Cell mass" of Adipose Tissue is very small (about 25 µL/g for adipocytes and 2 µL/g stromal, plus about 1 µL/g blood). This fact, translates into an extremely high (with respect to the actual "live cytoplasm" size) metabolic activity, which make WAT an even more significant agent in the control of energy metabolism.
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Oleoyl-estrone treatment reduces the volume of white Adipose Tissue Cells in the rat.
Journal of Physiology and Biochemistry, 2000Co-Authors: C. Cabot, J. A. Fernández-lópez, Marià AlemanyAbstract:It has been showed that oleoyl-estrone treatment diminishes the fat content of lean and obese rats. In this work it has been determined that oleoyl-estrone treatment diminishes white Adipose Tissue Cell size. Zucker Fa/? rats were implanted in the left carotid with miniosmotic pumps filled with either a fat stable emulsion (control) or supplemented with oleoyl-estrone (3.5 mmol/kg day, treated). After 14 days treatment, samples of inguinal subcutaneous and periovaric white Adipose Tissue were obtained. The results demonstrate that oleoyl-estrone significantly reduces the width and volume of adypocytes in both locations, which suggests that oleoyl-estrone induces a general increase in lipolysis.
