MLL1 Inhibition and Vitamin D Signaling Cooperate to Facilitate the Expanded Pluripotency State.

Zhang, H; Khoa, LTP; Mao, F; Xu, H; Zhou, B; Han, Y; O'Leary, M; Nusrat, A; Wang, L; Saunders, TL; Dou, Y

MLL1 Inhibition and Vitamin D Signaling Cooperate to Facilitate the Expanded Pluripotency State.

Zhang, H Khoa, LTP Mao, F Xu, H

Zhou, B Han, Y O'Leary, M Nusrat, A Wang, L Saunders, TL Dou, Y

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Cell Rep, 2019, 29, (9), pp. 2659-2671.e6
Issue Date:: 2019-11-26

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Field	Value	Language
dc.contributor.author	Zhang, H
dc.contributor.author	Khoa, LTP
dc.contributor.author	Mao, F
dc.contributor.author	Xu, H https://orcid.org/0000-0003-1129-5337
dc.contributor.author	Zhou, B
dc.contributor.author	Han, Y
dc.contributor.author	O'Leary, M
dc.contributor.author	Nusrat, A
dc.contributor.author	Wang, L
dc.contributor.author	Saunders, TL
dc.contributor.author	Dou, Y
dc.date.accessioned	2024-03-12T04:01:03Z
dc.date.available	2019-10-16
dc.date.available	2024-03-12T04:01:03Z
dc.date.issued	2019-11-26
dc.identifier.citation	Cell Rep, 2019, 29, (9), pp. 2659-2671.e6
dc.identifier.issn	2211-1247
dc.identifier.issn	2211-1247
dc.identifier.uri	http://hdl.handle.net/10453/176551
dc.description.abstract	Dynamic establishment of histone modifications in early development coincides with programed cell fate restriction and loss of totipotency beyond the early blastocyst stage. Causal function of histone-modifying enzymes in this process remains to be defined. Here we show that inhibiting histone methyltransferase MLL1 reprograms naive embryonic stem cells (ESCs) to expanded pluripotent stem cells (EPSCs), with differentiation potential toward both embryonic and extraembryonic lineages in vitro and in vivo. MLL1 inhibition or deletion upregulates gene signatures of early blastomere development. The function of MLL1 in restricting induction of EPSCs is mediated partly by Gc, which regulates cellular response to vitamin D signaling. Combined treatment of MLL1 inhibitor and 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) cooperatively enhanced functionality of EPSCs, triggering an extended 2C-like state in vitro and robust totipotent-like property in vivo. Our study sheds light on interplay between epigenetics and vitamin D pathway in cell fate determination.
dc.format	Print
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Cell Rep
dc.relation.isbasedon	10.1016/j.celrep.2019.10.074
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 1116 Medical Physiology
dc.subject.classification	31 Biological sciences
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Histone-Lysine N-Methyltransferase
dc.subject.mesh	Humans
dc.subject.mesh	Myeloid-Lymphoid Leukemia Protein
dc.subject.mesh	Pluripotent Stem Cells
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Vitamin D
dc.subject.mesh	Pluripotent Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Histone-Lysine N-Methyltransferase
dc.subject.mesh	Vitamin D
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Myeloid-Lymphoid Leukemia Protein
dc.subject.mesh	Cell Differentiation
dc.subject.mesh	Histone-Lysine N-Methyltransferase
dc.subject.mesh	Humans
dc.subject.mesh	Myeloid-Lymphoid Leukemia Protein
dc.subject.mesh	Pluripotent Stem Cells
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Vitamin D
dc.title	MLL1 Inhibition and Vitamin D Signaling Cooperate to Facilitate the Expanded Pluripotency State.
dc.type	Journal Article
utslib.citation.volume	29
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1116 Medical Physiology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-12T04:01:01Z
pubs.issue	9
pubs.publication-status	Published
pubs.volume	29
utslib.citation.issue	9

Abstract:

Dynamic establishment of histone modifications in early development coincides with programed cell fate restriction and loss of totipotency beyond the early blastocyst stage. Causal function of histone-modifying enzymes in this process remains to be defined. Here we show that inhibiting histone methyltransferase MLL1 reprograms naive embryonic stem cells (ESCs) to expanded pluripotent stem cells (EPSCs), with differentiation potential toward both embryonic and extraembryonic lineages in vitro and in vivo. MLL1 inhibition or deletion upregulates gene signatures of early blastomere development. The function of MLL1 in restricting induction of EPSCs is mediated partly by Gc, which regulates cellular response to vitamin D signaling. Combined treatment of MLL1 inhibitor and 1α,25-dihydroxyvitamin D3 (1,25-(OH)2D3) cooperatively enhanced functionality of EPSCs, triggering an extended 2C-like state in vitro and robust totipotent-like property in vivo. Our study sheds light on interplay between epigenetics and vitamin D pathway in cell fate determination.

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http://hdl.handle.net/10453/176551