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Title: Reprogramming towards totipotency is greatly facilitated by synergistic effects of small molecules
Authors: Miyamoto, Kei
Tajima, Yosuke
Yoshida, Koki
Oikawa, Mami
Azuma, Rika
Allen, George E.
Tsujikawa, Tomomi
Tsukaguchi, Tomomasa
Bradshaw, Charles R.
Jullien, Jerome
Yamagata, Kazuo
Matsumoto, Kazuya
Anzai, Masayuki
Imai, Hiroshi
Gurdon, John B.
Yamada, Masayasu
Author's alias: 宮本, 圭
山田, 雅保
Keywords: Nuclear transfer
Epigenetic modification
Issue Date: 2017
Publisher: The Company of Biologists
Journal title: Biology Open
Volume: 6
Start page: 415
End page: 424
Abstract: Animal cloning has been achieved in many species by transplanting differentiated cell nuclei to unfertilized oocytes. However, the low efficiencies of cloning have remained an unresolved issue. Here we find that the combination of two small molecules, trichostatin A (TSA) and vitamin C (VC), under culture condition with bovine serum albumin deionized by ion-exchange resins, dramatically improves the cloning efficiency in mice and 15% of cloned embryos develop to term by means of somatic cell nuclear transfer (SCNT). The improvement was not observed by adding the non-treated, rather than deionized, bovine serum. RNA-seq analyses of SCNT embryos at the two-cell stage revealed that the treatment with TSA and VC resulted in the upregulated expression of previously identified reprogramming-resistant genes. Moreover, the expression of early-embryo-specific retroelements was upregulated by the TSA and VC treatment. The enhanced gene expression was relevant to the VC-mediated reduction of histone H3 lysine 9 methylation in SCNT embryos. Our study thus shows a simply applicable method to greatly improve mouse cloning efficiency, and furthers our understanding of how somatic nuclei acquire totipotency.
Description: クローン動物の発生率の劇的な改善に成功--培養条件の改善のみで安定したクローンマウスの作出が可能に--. 京都大学プレスリリース. 2017-04-17.
Rights: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
URI: http://hdl.handle.net/2433/219613
DOI(Published Version): 10.1242/bio.023473
Related Link: http://www.kyoto-u.ac.jp/ja/research/research_results/2017/170415_1.html
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