SHP-1 arrests mouse early embryo development through downregulation of Nanog by dephosphorylation of STAT3.
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.
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Songna
S
Yin
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Haibo
H
Wu
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Jiaxing
J
Lv
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Xinying
X
Wu
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Yan
Y
Zhang
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China ; College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
Juan
J
Du
College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China ; Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, China.
Yong
Y
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D054278:Embryonal Carcinoma Stem Cells; D047108:Embryonic Development / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D000071317:Nanog Homeobox Protein; D010766:Phosphorylation / Q000235:genetics*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse