TY - JOUR
T1 - β-Catenin Functions Pleiotropically in Differentiation and Tumorigenesis in Mouse Embryo-Derived Stem Cells
AU - Okumura, Noriko
AU - Akutsu, Hidenori
AU - Sugawara, Tohru
AU - Miura, Takumi
AU - Takezawa, Youki
AU - Hosoda, Akihiro
AU - Yoshida, Keiichi
AU - Ichida, Justin K.
AU - Yamada, Mitsutoshi
AU - Hamatani, Toshio
AU - Kuji, Naoaki
AU - Miyado, Kenji
AU - Yoshimura, Yasunori
AU - Umezawa, Akihiro
PY - 2013/5/14
Y1 - 2013/5/14
N2 - The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-catΔ/Δ) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-catΔ/Δ ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.
AB - The canonical Wnt/β-catenin signaling pathway plays a crucial role in the maintenance of the balance between proliferation and differentiation throughout embryogenesis and tissue homeostasis. β-Catenin, encoded by the Ctnnb1 gene, mediates an intracellular signaling cascade activated by Wnt. It also plays an important role in the maintenance of various types of stem cells including adult stem cells and cancer stem cells. However, it is unclear if β-catenin is required for the derivation of mouse embryo-derived stem cells. Here, we established β-catenin-deficient (β-catΔ/Δ) mouse embryo-derived stem cells and showed that β-catenin is not essential for acquiring self-renewal potential in the derivation of mouse embryonic stem cells (ESCs). However, teratomas formed from embryo-derived β-catΔ/Δ ESCs were immature germ cell tumors without multilineage differentiated cell types. Re-expression of functional β-catenin eliminated their neoplastic, transformed phenotype and restored pluripotency, thereby rescuing the mutant ESCs. Our findings demonstrate that β-catenin has pleiotropic effects in ESCs; it is required for the differentiation of ESCs and prevents them from acquiring tumorigenic character. These results highlight β-catenin as the gatekeeper in differentiation and tumorigenesis in ESCs.
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U2 - 10.1371/journal.pone.0063265
DO - 10.1371/journal.pone.0063265
M3 - Article
C2 - 23691006
AN - SCOPUS:84877744686
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 5
M1 - e63265
ER -