{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":[null],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-15009"],"description":["Single-nuclei RNA sequencing (snRNA-seq) data of human muscle cells. The samples are a part of a study investigating the effect of one-legged high-intensity interval training (HIIT) on the nuclear transcriptional response in skeletal muscle. The HIIT was done on one leg on a cycle ergometer, and vastus lateralis muscle biopsies were obtained from both the untrained and trained leg following the two weeks training protocol. The study contains samples from 9 people with Type 2 Diabetes (T2D) and 10 samples from a Body Mass Index (BMI) and age matched control group without diabetes. The experimental study is described in: Dela et al., Acta Physiol, 2019. The snRNA-seq data contains nuclei isolated from 38 available biopsies with the following conditions: Control-Trained, Control-Untrained, Diabetes-Trained, Diabetes-Untrained."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sequencing - The libraries were sequenced on an Illumina NextSeq550 using NextSeq 500/550 High Output Kit v2.5 (150 Cycles) with up to 400M reads according to the manufacturer’s instructions. The nuclei were loaded with one NextSeq550 kit per participant, thus loading the untrained and trained sample on the same chip. There were 200M reads per sample. The sequencing was done with 28 cycles (10X x Index and UMI), 8 cycles (i7 Index), 0 cycles (i5 Index), and 91 cycles for the reads.","Library Construction - For isolation of single-nucleus RNA, the samples were run using the 10X Genomics Chromium Next GEM Single Cell 3ʹ Reagent Kits v3.1 on a 10X Chromium Controller according to manufacturer’s instructions (protocol version “CG000204_ChromiumNextGEMSingleCell3_v3.1_Rev_D”)","Sample Collection - The muscle biopsies have already be analysed in a previous study (Dela et al., Acta Physiol (Oxf), 2019, doi: 10.1111/apha.13245. Epub 2019 Feb 14. PMID: 30585698). In summary, ten sedentary males with T2D and ten healthy males matched for age, body mass index (BMI), and peak oxygen uptake (V̇O2peak) performed two weeks (eight sessions) of one-legged HIIT on a bicycle ergometer. Each session included ten 1-minute intervals at >80% of maximal heart rate, interspersed with one minute of rest. Forty hours after the last exercise bout, lateral vastus muscle biopsies from the trained and untrained legs were obtained.","Nucleic Acid Extraction - Nuclei were isolated using a modified version of the Nuclei Isolation Kit: Nuclei PURE Prep, cat. no. NUC201 from Sigma-Aldrich. The entire protocol was carried out on ice. The tissue was lysed in ice-cold lysis buffer (Nuclei Pure Lysis Buffer, Sigma cat. no. L9286, with 1 mM DL-Dithiothreitol (DTT), Sigma cat. no. D9779, and 0.01% Triton X-100, Sigma cat. no. T1565). Homogenized for 30 seconds using an ULTRA-TURRAK TP18/10 homogenizer (20,000 rpm) for 10 minutes and filtered. Nuclei were pelleted by centrifugation and washed in wash buffer (1x DPBS, no calcium, no magnesium, Gibco cat. No. 14190, with 1% Human Serum Albumin Sigma cat. No. A1887, and 0.2 u/µL RNasin Plus RNase Inhibitor [40 u/µL], Promega cat. No. 2611). The lysate was then mixed with 1.8 M Su-crose Cushion Solution (mix of Nuclei PURE 2 M Sucrose Cushion Solution, Sigma cat. no. S9308, Nuclei PURE Sucrose Cushion Solution, Sigma cat. no. S9058 and 0.83 mM DTT). The mixture was then loaded on top of 1.8 M Sucrose Cushion Solution, and centrifuged. The supernatant was re-moved and nuclei-containing pellet was resuspended, centrifuged and filtered. The final pellet was resuspended in approximately 200 µL wash buffer and counted using NucleoCounter NC-200 (ChemoMetec cat. no. 900-0201) to determine nuclei concentration."],"figure_sub":["MINSEQE Score","Assays and Data","Processed Data","organisation","MAGE-TAB Files"],"data_protocol":["Data Transformation - The mapped cellranger count matrices were decontaminated for ambient RNA using SoupX (Young & Behjati, Gigascience, 2020,doi: 10.1093/gigascience/giaa151. PMID: 33367645;) with the automatically detected threshold.  Seurat V4 (Hao et al. Cell. 2021 doi: 10.1016/j.cell.2021.04.048. PMID: 34062119) was applied to each individual sample library, we ran normalization (NormalizeData), feature selection (FindVariableFeatures), scaling (ScaleData), and PCA (RunPCA) separately before hierarchically merging the datasets using Seurat. The integration was done using the Seurat function FindIntegrationAnchors and IntegrateData."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["NextSeq 550"],"pubmed_abstract":["Training can improve insulin sensitivity in individuals with type 2 diabetes, but a clear understanding of the mechanisms remains elusive. To further our knowledge in this area, we aimed to examine the effect of type 2 diabetes and of high-intensity interval training (HIIT) on the nuclear transcriptional response in skeletal muscle. We performed single-nucleus RNA-sequencing (snRNA-seq) and immunofluorescence analysis on muscle biopsies from the trained and the untrained legs of participants with and without type 2 diabetes, after 2 weeks of one-legged HIIT on a cycle ergometer. Surprisingly, the type 2 diabetes condition only seemed to have a minor effect on transcriptional activity in myonuclei related to major metabolic pathways when comparing the untrained legs. However, while in particular the type IIA myonuclei in the control group displayed a considerable metabolic response to HIIT, with increases in genes related to glycogen breakdown and glycolysis primarily in the type IIA myonuclei of the trained leg, this response was blunted in the diabetes group, despite a marked increase in glucose clearance in both groups. Additionally, we observed that fibre type distribution assessed by immunofluorescence significantly correlated with the proportion of myonuclei in the snRNA-seq analysis. In conclusion, the type 2 diabetes condition blunts the metabolic transcriptional response to HIIT in the type IIA myonuclei without affecting the improvement in insulin sensitivity. Additionally, our results indicate that snRNA-seq can be used as a surrogate marker for fibre type distribution in sedentary middle-aged adults. KEY POINTS: The study utilized single-nucleus RNA sequencing (snRNA-seq) to analyse 38 skeletal muscle biopsies, revealing distinct transcriptional profiles in myonuclei from individuals with and without type 2 diabetes (T2D) after 2 weeks of HIIT. snRNA-seq identified significant differences in gene expression, with 14 differentially expressed genes (DEGs) in type IIA myonuclei of the control group, specifically related to glycogen breakdown and glycolysis, which were blunted in the T2D group. In the control group, HIIT induced a substantial transcriptional response in type IIA myonuclei, enhancing metabolic pathways associated with insulin sensitivity, while the T2D group showed minimal transcriptional changes despite improved insulin sensitivity. The T2D group exhibited a blunted response in metabolic gene expression, indicating that the training effect on muscle adaptation was significantly impaired compared to healthy controls. Overall, the findings highlight the differential impact of HIIT on muscle metabolism, emphasizing the need for tailored exercise interventions for individuals with T2D."],"study_type":["single nucleus RNA sequencing"],"species":["Homo sapiens"],"pubmed_title":["The skeletal muscle response to high-intensity training assessed by single-nucleus RNA-sequencing is blunted in individuals with type 2 diabetes"],"additional_accession":["ERP171269"],"pubmed_authors":["Maria Hansen, Julius Elliot Raagaard Grothen, Anders Karlsen, Jaime Moreno Martinez, Nikos Sidiropoulos, Jørn Wulff Helge, Thomas Åskov Pedersen, Flemming Dela","Thomas Åskov Pedersen"]},"is_claimable":false,"name":"Trained and untrained human skeletal muscle single-nucleus RNA-sequencing from individuals with type 2 diabetes and control","description":"Single-nuclei RNA sequencing (snRNA-seq) data of human muscle cells. The samples are a part of a study investigating the effect of one-legged high-intensity interval training (HIIT) on the nuclear transcriptional response in skeletal muscle. The HIIT was done on one leg on a cycle ergometer, and vastus lateralis muscle biopsies were obtained from both the untrained and trained leg following the two weeks training protocol. The study contains samples from 9 people with Type 2 Diabetes (T2D) and 10 samples from a Body Mass Index (BMI) and age matched control group without diabetes. The experimental study is described in: Dela et al., Acta Physiol, 2019. The snRNA-seq data contains nuclei isolated from 38 available biopsies with the following conditions: Control-Trained, Control-Untrained, Diabetes-Trained, Diabetes-Untrained.","dates":{"release":"2025-04-24T00:00:00Z","modification":"2026-05-27T12:50:30.498Z","creation":"2025-04-04T10:41:30.637Z"},"accession":"E-MTAB-15009","cross_references":{"ENA":["ERP171269"],"EFO":["EFO_0002944","EFO_0004170","EFO_0009809","EFO_0005518","EFO_0003816","EFO_0004184"],"doi":["10.1113/JP288368"]}}