Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency

doi:10.1016/j.stem.2018.07.004

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	Mor, Nofar 1; Rais, Yoach 1; Sheban, Daoud 1,2; Peles, Shani 1; Aguilera-Castrejon, Alejandro 1; Zviran, Asaf 1,3; Elinger, Dalia 4; Viukov, Sergey 1; Geula, Shay 1; Krupalnik, Vladislav 1; Zerbib, Mirie 1; Chomsky, Elad 5; Lasman, Lior 1; Shani, Tom 1; Bayerl, Jonathan 1; Gafni, Ohad 1; Hanna, Suhair 6; Buenrostro, Jason D.7,8; Hagai, Tzachi 9; Masika, Hagit 10; Vainorius, Gintautas 11; Bergman, Yehudit 12; Greenleaf, William J.12,13; Esteban, Miguel A.14,15; Elling, Ulrich ; Levin, Yishai ; Massarwa, Rada 1; Merbl, Yifat 2; Novershtern, Noa 1; Hanna, Jacob H.1
	Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency
刊名	CELL STEM CELL
ISSN号	1934-5909
	2018-09-06
卷号	23 期号:3 页码:412-+
DOI	10.1016/j.stem.2018.07.004
语种	英语
WOS研究方向	Cell Biology
摘要	Mbd3, a member of nucleosome remodeling and deacetylase (NuRD) co-repressor complex, was previously identified as an inhibitor for deterministic induced pluripotent stem cell (iPSC) reprogramming, where up to 100% of donor cells successfully complete the process. NuRD can assume multiple mutually exclusive conformations, and it remains unclear whether this deterministic phenotype can be attributed to a specific Mbd3/NuRD subcomplex. More-over, since complete ablation of Mbd3 blocks somatic cell proliferation, we aimed to explore functionally relevant alternative ways to neutralize Mbd3-dependent NuRD activity. We identify Gatad2a, a NuRD-specific subunit, whose complete deletion specifically disrupts Mbd3/NuRD repressive activity on the pluripotency circuitry during iPSC differentiation and reprogramming without ablating somatic cell proliferation. Inhibition of Gatad2a facilitates deterministic murine iPSC reprogramming within 8 days. We validate a distinct molecular axis, Gatad2a-Chd4-Mbd3, within Mbd3/NuRD as being critical for blocking reestablishment of naive pluripotency and further highlight signaling-dependent and post-translational modifications of Mbd3/NuRD that influence its interactions and assembly.
WOS记录号	WOS:000443851400015
收录类别	SCI
引用统计
文献类型	期刊论文
条目标识符	http://ir.gig.ac.cn/handle/344008/39759
通讯作者	Rais, Yoach; Novershtern, Noa; Hanna, Jacob H.
作者单位	1.Weizmann Inst Sci, Dept Mol Genet, 234 Herzl, IL-76100 Rehovot, Israel 2.Weizmann Inst Sci, Dept Immunol, Rehovot, Israel 3.New York Genome Ctr, New York, NY USA 4.Weizmann Inst Sci, Nancy & Stephen Grand Israel Natl Ctr Personalize, Rehovot, Israel 5.Weizmann Inst Sci, Dept Regulat Biol, Rehovot, Israel 6.Rambam Hlth Care Campus, Dept Pediat, Haifa, Israel 7.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA 8.Harvard Univ, Harvard Soc Fellows, Cambridge, MA 02138 USA 9.Wellcome Genome Campus, EMBL European Bioinformat Inst, Cambridge, England 10.Hebrew Univ Jerusalem, Dept Dev Biol & Canc Res, Jerusalem, Israel 11.Inst Mol Biotechnol IMBA, Vienna, Austria 12.Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA 13.Chan Zuckerberg Biohub, San Francisco, CA USA 14.Chinese Acad Sci, Guangzhou Inst Biomed, Key Lab Regenerat Biol, Guangzhou, Guangdong, Peoples R China 15.Chinese Acad Sci, Guangzhou Inst Hlth, Guangzhou, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Mor, Nofar,Rais, Yoach,Sheban, Daoud,et al. Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency[J]. CELL STEM CELL,2018,23(3):412-+.
APA	Mor, Nofar.,Rais, Yoach.,Sheban, Daoud.,Peles, Shani.,Aguilera-Castrejon, Alejandro.,...&Hanna, Jacob H..(2018).Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency.CELL STEM CELL,23(3),412-+.
MLA	Mor, Nofar,et al."Neutralizing Gatad2a-Chd4-Mbd3/NuRD Complex Facilitates Deterministic Induction of Naive Pluripotency".CELL STEM CELL 23.3(2018):412-+.