Original Article

Somatostatin receptor type 2 contributes to the self-renewal of murine embryonic stem cells

Authors: Xin-xiu XU, Li-hong ZHANG, Xin XIE
DOI: 10.1038/aps.2014.51

Abstract

Xin-xiu XU1, 2, Li-hong ZHANG1, *, Xin XIE1, 2, *
1CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; 2Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China

Aim: The roles of G-protein coupled receptors (GPCRs) in stem cell biology remain unclear. In this study, we aimed to identify GPCRs that might contribute to the self-renewal of mouse embryonic stem cells (mESCs).

Methods: The expression levels of pluripotent genes and GPCR gene were detected in E14 mESCs using PCR array and RT-PCR. Immunofluorescent staining was used to examine the expression of pluripotent markers and the receptor translocation. Western blot analysis was used to detect phosphorylation of signal proteins. Knock-down of receptor was conducted to confirm its role in pluripotency maintenance.

Results: In leukemia inhibitory factor (LIF)-free medium, mESCs lost the typical morphology of pluripotency, accompanied by markedly decreases in expression of somatostatin receptor type 2 (SSTR2), as well as the pluripotency biomarkers Oct4, Sox2, Rex1 and Nanog. Addition of the SSTR2 agonist octreotide or seglitide (0.1–30 μmol/L) in LIF-free medium dose-dependently promoted the self-renewal of mESCs, whereas the SSTR2 antagonist S4 (0.03–3 μmol/L) dose-dependently blocked octreotide-induced self-renewal. Knock-down of SSTR2 significantly decreased the self-renewal of mESCs even in the presence of LIF. Addition of LIF (1000 U/mL) or octreotide (1 μmol/L) in LIF-free medium significantly increased both phosphorylation and nuclear localization of STAT3.

Conclusion: The activation of SSTR2 contributes to the self-renewal of mESCs via activation of the STAT3 pathway.


Keywords: stem cell; mouse embryonic stem cell; GPCR; somatostatin receptor type 2; self-renewal; STAT3; leukemia inhibitory factor; octreotide; seglitide

This project was supported by grants from the Chinese Academy of Sciences (XDA01040301), the National Natural Science Foundation of China (No 31371511), Ministry of Science and Technology of China (No 2013ZX09507001, 2012ZX09301001-005), and Shanghai Commission of Science and Technology (No 12XD1402100).
* To whom correspondence should be addressed.
E-mail biochemzhang@hotmail.com (Li-hong ZHANG); xxie@simm.ac.cn (Xin XIE)
Received 2014-02-12 Accepted 2014-05-23
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