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| Status |
Public on Jul 27, 2022 |
| Title |
Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [scRNA-seq_Hepatocyte] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The liver stores glycogen and releases blood glucose and is therefore essential for glucose metabolism. Group 2 innate lymphoid cells (ILC2s) in adipose and pancreatic tissues are involved in glucose homeostasis, but the metabolic contribution of liver ILC2s remains unclear. Herein, we show that interleukin (IL)-33 treatment induced IL-13 production in liver ILC2s, which consequently reduced blood glucose levels. IL-13 also directly suppressed gluconeogenesis in primary hepatocytes. Single-cell RNA sequencing (scRNA-seq) and cell-cell interaction analysis in liver ILC2s and hepatocytes demonstrated that IL-33 administration suppressed gluconeogenesis in a specific Hnf4a/G6pchigh-hepatocyte cluster involving expression of Stat3, which significantly interacted with liver ILC2s via IL-13/IL-13 receptor signaling. To address the regulatory mechanism underlying IL-13 production in liver ILC2s, we performed GATA3 transcriptional complex analysis, and GATA3-ChIP-seq, ATAC-seq, and scRNA-seq trajectory analyses, focusing on GATA3-interacting proteins that were functionally specific in ILC2s. AP-1 family members were found to suppress the induction of IL-13 in liver ILC2s. Thus, our study revealed a novel role for liver ILC2s in glucose homeostasis.
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| Overall design |
Gene expression levels of primary hepatocyte from PBS-treated or IL-33 treated mice were evaluted using single cell RNA-seq.
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| Contributor(s) |
Fujimoto M, Eunyoung L, Hatano R, Miki T, Tanaka T |
| Citation(s) |
36109558 |
| |
| Submission date |
Nov 21, 2021 |
| Last update date |
Sep 27, 2022 |
| Contact name |
Masanori Fujimoto |
| E-mail(s) |
fujimoto212@gmail.com
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| Organization name |
Chiba University
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| Department |
Graduate School of Medicine
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| Lab |
1. Department of Molecular Diagnosis, 2. Department of Endocrinology, Hematology and Gerontology
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| Street address |
Inohana 1-8-1
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| City |
Chiba-city |
| State/province |
Chiba-prefecture |
| ZIP/Postal code |
260-8677 |
| Country |
Japan |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE189287 |
Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling |
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| Relations |
| BioProject |
PRJNA782349 |
| SRA |
SRP347118 |
