GSE172148: RNA sequencing of control and PTPN2 knocked down transcriptomes in EndoC-𝛽H1 cells with or without the treatment of pro-inflammatory cytokines

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GROUP CONDITION SAMPLES
EndoC-𝛽H1 cells
GSM5242716 GSM5242722 GSM5242728
GSM5242719 GSM5242725 GSM5242731
GSM5242718 GSM5242724 GSM5242730
GSM5242721 GSM5242727 GSM5242733
GSM5242720 GSM5242726 GSM5242732
GSM5242717 GSM5242723 GSM5242729
Description

Submission Date: Apr 15, 2021

Summary: Type 1 diabetes (T1D) results from autoimmune destruction of β-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas from diabetic NOD mice treated with anti-CD3 monoclonal antibody and IL-1 receptor antagonist (IL-1RA). The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in islets from mice with reversed diabetes. To address the functional role of PTPN2 in β-cells, we generated PTPN2 deficient stem cell-derived β-like and human EndoC-βH1 cells. Mechanistically, we demonstrated that PTPN2 inactivation in β-cells exacerbates the type I and type II IFN signalling networks, and the potential progression towards autoimmunity. Moreover, we established the capacity of PTPN2 to modulate the Ca2+-dependent unfolded protein response in β-cells. Adenovirus-induced overexpression of PTPN2 decreased BiP expression and partially protected from ER-stress induced β-cell death. Our results postulate PTPN2 as a key protective factor in β-cells during inflammation and ER stress in autoimmune diabetes.

GEO Accession ID: GSE172148

PMID: 35044456

Description

Submission Date: Apr 15, 2021

Summary: Type 1 diabetes (T1D) results from autoimmune destruction of β-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas from diabetic NOD mice treated with anti-CD3 monoclonal antibody and IL-1 receptor antagonist (IL-1RA). The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in islets from mice with reversed diabetes. To address the functional role of PTPN2 in β-cells, we generated PTPN2 deficient stem cell-derived β-like and human EndoC-βH1 cells. Mechanistically, we demonstrated that PTPN2 inactivation in β-cells exacerbates the type I and type II IFN signalling networks, and the potential progression towards autoimmunity. Moreover, we established the capacity of PTPN2 to modulate the Ca2+-dependent unfolded protein response in β-cells. Adenovirus-induced overexpression of PTPN2 decreased BiP expression and partially protected from ER-stress induced β-cell death. Our results postulate PTPN2 as a key protective factor in β-cells during inflammation and ER stress in autoimmune diabetes.

GEO Accession ID: GSE172148

PMID: 35044456

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