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Series GSE234704 Query DataSets for GSE234704
Status Public on Jan 18, 2024
Title Single-cell RNA sequencing reveals preserved pancreatic endocrine cell identity and function by administration of a metabolite-based diet in autoimmune diabetes
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Objective: An altered gut bacterial composition is associated with the pathogenesis of type 1 diabetes and short-chain fatty acids are known to play a pivotal role in maintaining gut homeostasis. The effects of short-chain fatty acids on pancreatic islet cell function, insulin production and local immune-infiltration, however, remain elusive.Methods: Five-week-old female NOD mice were fed with an acetylated and butyrylated high-amylose maize-resistant starch (HAMSAB) or control diet for five consecutive weeks. The pancreata were harvested, islets isolated using collagenase, and dispersed into single cells by trypsin. Single-cell RNA sequencing was performed with 10x Chromium. The raw counts were analysed using RStudio with the Seurat package. Human embryonic stem cell-differentiated beta-like cells, mouse islets and INS-1E beta cell line were treated with acetate, butyrate and/or combination. Pro-inflammatory cytokines (IFN- + IL-1) were used for stress response and viability assays. Results: single-cell RNA sequencing analysis mapped the gene expression profiles of 4,301 and 4,113 individual islet cells from HAMSAB or HAMS fed mice, respectively. Cells were annotated into 11 clusters: 5 immune, 4 endocrine, acinar and endothelial cell types. The scRNA seq dataset indicated that T cells, B cells, macrophages, and dendritic cell subsets infiltrated the islets of Langerhans from both HAMSAB and HAMS-fed mice. Interestingly, HAMSAB induced an immune tolerogenic profile and lower cytotoxic Gzma+ CD8+ T cells. Moreover, HAMSAB maintained the expression of beta cell functional genes (i.e., Ins1, Ins2, G6pc2, Prlr and Iapp) and decreased the expression of genes associated with cellular stress (i.e., Fos, Impact, Stat1, Dusp1 and Hsp40/Dnajb1). Short-chain fatty acid treatment decreased pro-inflammatory cytokine-induced stress in mouse islets and INS-1E beta cells. In addition, HAMSAB preserved the identity of endocrine cells, evaluated by a decrease in dedifferentiated poly-hormonal cells expressing endocrine progenitor genes (MafA, Nfix). Importantly, short-chain fatty acids increased insulin levels in human embryonic stem cell-differentiated beta-like cells and improve transplantation outcome in NOD/SCID mice. Conclusions: Short-chain fatty acids prevent diabetes development in NOD mice, at least in part, by enhancing beta cell function and preserving the cell identity of endocrine cells under inflammatory-mediated autoimmune stress.
 
Overall design Single-cell RNA-Seq of mouse pancreata fed with HAMS or HAMSAB diet
 
Contributor(s) Vandenbempt V, Eski SE, Brahma M, Li A, Negueruela J, Bruggeman Y, Demine S, Xiao P, Cardozo A, Baeyens N, Martelotto L, Singh SP, Mariño E, Gysemans C, Gurzov E
Citation(s) 38213620
Submission date Jun 12, 2023
Last update date Jan 19, 2024
Contact name Valerie Vandenbempt
E-mail(s) Valerie.vandenbempt@ulb.be
Phone 0032497208111
Organization name Université Libre de Bruxelles
Lab Signal Transduction and Metabolism Laboratory
Street address Lenniksebaan 808
City Anderlecht
State/province Vlaams-Brabant
ZIP/Postal code 1070
Country Belgium
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (2)
GSM7473558 HAMS, scRNAseq
GSM7473559 HAMSAB, scRNAseq
Relations
BioProject PRJNA982793

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE234704_Alpha_DEG_diet.csv.gz 1.6 Kb (ftp)(http) CSV
GSE234704_Beta_DEG_diet.csv.gz 3.1 Kb (ftp)(http) CSV
GSE234704_Delta_DEG_diet.csv.gz 1.2 Kb (ftp)(http) CSV
GSE234704_RAW.tar 15.7 Mb (http)(custom) TAR (of MTX, TSV)
GSE234704_bcells_DEG_diet.csv.gz 792 b (ftp)(http) CSV
GSE234704_cdc_DEG_diet.csv.gz 3.2 Kb (ftp)(http) CSV
GSE234704_mf_DEG_diet.csv.gz 2.0 Kb (ftp)(http) CSV
GSE234704_pdc_DEG_diet.csv.gz 470 b (ftp)(http) CSV
GSE234704_tcells_DEG_diet.csv.gz 1.9 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data provided as supplementary file

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