SHP-1 Arrests Mouse Early Embryo Development through Downregulation of Nanog by Dephosphorylation of STAT3

Abstract

Src-homology protein tyrosine phosphatase-1 (SHP-1) is a protein tyrosine phosphatase that is implicated in the regulation of growth, differentiation, survival, apoptosis and proliferation of hematopoietic cells and other cell types. Here, we found that SHP-1 is involved in regulation of early embryonic development. Embryos overexpressing SHP-1 were mainly arrested at the 8-cell stage, and Nanog mRNA expression was first observed in the morulae that showed down-regulation of SHP-1. These results suggested an antagonistic relationship between SHP-1 and Nanog during early embryonic development. Next, the specific mechanism was examined in mouse F9 embryonal carcinoma cells. We confirmed that signal transducer and activator of transcription 3 (STAT3) was a substrate for SHP-1 by co-immunoprecipitation. Using overexpression and knockdown strategies, we found that SHP-1 participated in regulation of Nanog expression. Furthermore, site mutation of STAT3 was performed to confirm that SHP-1 was responsible for rapid STAT3 dephosphorylation and a decrease of Nanog expression in F9 cells. These findings suggest that SHP-1 plays a crucial role during early embryonic development. Thus, SHP-1 may function as a key regulator for Nanog that specifically demarcates the nascent epiblast, coincident with the domain of X chromosome reprogramming.

Expression of IFNAR1 and IFNAR2 in cattle placenta during early pregnancy

“…Then, the cDNA was transcribed using Reverse Transcription Kits (TransStart Green qPCR SuperMix, Beijing, China) following the instructions. Subsequently, the cDNAs were frozen at −20°C (Yin et al., ). The mRNA expression for IFNAR1, IFNAR2 and GADPH was assessed by RT‐qPCR using an ABI StepOnePlus PCR System (Applied Biosystem, Foster City, CA, USA) with SYBR Primix ExTaq II (TransStart).…”

Role of STAT3 in Genesis and Progression of Human Malignant Gliomas

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