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Single-nucleus RNA sequencing of human subcutaneous adipose tissue biopsies from 16 Finnish participants.

ABSTRACT: Single-nucleus RNA-seq was performed to characterize the transcriptomes of cell types in human subcutaneous adipose tissue. Biopsies from 16 Finnish participants from the Finnish Twin Study and CRYO study were included.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236708 | GEO | 2023/07/22

REPOSITORIES: GEO

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Project description:Background Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the whole-genome scale patterns of these changes or about their variation between different obesity subgroups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics. Methods We analyzed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of SAT in young MZ twin pairs (n =26, intrapair difference in BMI>3 kg/m2, aged 23-36), from 10 birth cohorts of adult Finnish twins. The clinical data included measurements of body composition, insulin resistance, lipids, and adipokines. Results We found 2108 genes differentially expressed (FDR<0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes revealed a significant downregulation of mitochondrial oxidative pathways (p<0.05) and upregulation of inflammation pathways (p<0.05). Hierarchical clustering of heavy/lean twin ratios, representing effects of acquired obesity in the transcriptomics data, revealed three sub-groups with different molecular profiles (FDR<0.05). Analyses comparing these sub-groups showed that, in the heavy co-twins, downregulation of the mitochondrial pathways, especially that of branched chain amino acid (BCAA) degradation was more evident in two last clusters while and upregulation of the inflammatory response was most evident in the last, presumably the unhealthiest cluster. High fasting insulin levels and large adipocyte diameter were the predominant clinical characteristic of the heavy co-twins in this cluster (Bonferroni adjusted p<0.05). Conclusions This is the first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based on both SAT gene expression profiles and clinical traits. We conclude that a decrease in mitochondrial BCAA degradation and an increase in inflammation in SAT co-occur and associate with hyperinsulinemia and large adipocyte size in unhealthy obesity.

Project description:Background Bordetella pertussis is a Gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. Methodology/Principal Findings The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of the genome of Tohama I, the strain of which the genome has been sequenced [21]. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared to the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to ion transport, metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. Conclusion/Significance Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations. Keywords: comparetive genomic hybridisation

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Single-nucleus RNA sequencing of human subcutaneous adipose tissue biopsies from 16 Finnish participants.

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