The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells

Hideaki Naoe; Tatsuyuki Chiyoda; Jo Ishizawa; Kenta Masuda; Hideyuki Saya; Shinji Kuninaka

doi:10.1016/j.bbrc.2012.11.075

The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells

Hideaki Naoe, Tatsuyuki Chiyoda, Jo Ishizawa, Kenta Masuda, Hideyuki Saya, Shinji Kuninaka

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1^GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1^GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.

Original language	English
Pages (from-to)	757-762
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	430
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2012.11.075
Publication status	Published - 2013 Jan 11

Keywords

APC/C
Cdh1
Endocycle
G2/M transition
Trophoblast giant cell
Trophoblast stem cell

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2012.11.075

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title = "The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells",

abstract = "Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.",

keywords = "APC/C, Cdh1, Endocycle, G2/M transition, Trophoblast giant cell, Trophoblast stem cell",

author = "Hideaki Naoe and Tatsuyuki Chiyoda and Jo Ishizawa and Kenta Masuda and Hideyuki Saya and Shinji Kuninaka",

note = "Funding Information: We thank Drs. G. Leone and P. L. Wenzel for providing in situ hybridization probes; N. Tomotsugu for assistance in the statistical analyses; I. Ishimatsu for technical assistance in the histological analysis; T. Shinoda for technical assistance in the analysis of nuclear size; N. Suzuki for animal maintenance; and K. Arai for secretarial assistance. This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (to S.K. ( 20058033 ) and H.S. ( 17013070 )).",

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AU - Ishizawa, Jo

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AU - Saya, Hideyuki

AU - Kuninaka, Shinji

N1 - Funding Information: We thank Drs. G. Leone and P. L. Wenzel for providing in situ hybridization probes; N. Tomotsugu for assistance in the statistical analyses; I. Ishimatsu for technical assistance in the histological analysis; T. Shinoda for technical assistance in the analysis of nuclear size; N. Suzuki for animal maintenance; and K. Arai for secretarial assistance. This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (to S.K. ( 20058033 ) and H.S. ( 17013070 )).

PY - 2013/1/11

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N2 - Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.

AB - Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1GT/GT) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1GT/GT TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation.

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KW - Trophoblast stem cell

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The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells

Abstract

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