ERas is expressed in primate embryonic stem cells but not related to tumorigenesis.
The ERas gene promotes the proliferation of and formation of teratomas by mouse embryonic stem (ES) cells. However, its human orthologue is not expressed in human ES cells. This implies that the behavior of transplanted mouse ES cells would not accurately reflect the behavior of transplanted human ES cells and that the use of nonhuman primate models might be more appropriate to demonstrate the safety of human ES cell-based therapies. However, the expression of the ERas gene has not been examined in nonhuman primate ES cells. In this study, we cloned the cynomolgus homologue and showed that the ERas gene is expressed in cynomolgus ES cells. Notably, it is also expressed in cynomolgus ES cell-derived differentiated progeny as well as cynomolgus adult tissues. The ERas protein is detectable in various cynomolgus tissues as assessed by immunohistochemisty. Cynomolgus ES cell-derived teratoma cells, which also expressed the ERas gene at higher levels than the undifferentiated cynomolgus ES cells, did not develop tumors in NOD/Shi-scid, IL-2Rgamma(null) (NOG) mice. Even when the ERas gene was overexpressed in cynomolgus stromal cells, only the plating efficiency was improved and the proliferation was not promoted. Thus, it is unlikely that ERas contributes to the tumorigenicity of cynomolgus cells. Therefore, cynomolgus ES cells are more similar to human than mouse ES cells despite that ERas is expressed in cynomolgus and mouse ES cells but not in human ES cells.
Tanaka
Yujiro
Y
Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; Department of Pediatric Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Ikeda
Tamako
T
Kishi
Yukiko
Y
Masuda
Shigeo
S
Shibata
Hiroaki
H
Takeuchi
Kengo
K
Komura
Makoto
M
Iwanaka
Tadashi
T
Muramatsu
Shin-Ichi
S
Kondo
Yasushi
Y
Takahashi
Kazutoshi
K
Yamanaka
Shinya
S
Hanazono
Yutaka
Y
D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D009928:Organ Specificity; D013045:Species Specificity; D013724:Teratoma / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
C474774:ERas protein, human; C474773:ERas protein, mouse; D015689:Oncogene Protein p21(ras)