Respuela, Patricia ORCID: 0000-0002-9719-7860, Nikolic, Milos ORCID: 0000-0003-0029-7601, Tan, Minjia ORCID: 0000-0002-6784-9653, Frommolt, Peter ORCID: 0000-0002-1966-8014, Zhao, Yingming, Wysocka, Joanna and Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 (2016). Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification. Cell Stem Cell, 18 (1). S. 118 - 134. CAMBRIDGE: CELL PRESS. ISSN 1875-9777

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Abstract

Following implantation, mouse epiblast cells transit from a naive to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for exit from naive pluripotency and progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naive pluripotency expression program through decommissioning of active enhancers associated with key naive pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow re-activation of relevant genes required for proper PGC specification. Our findings therefore uncover a cycle of activation and deactivation of Foxd3 required for exit from naive pluripotency and subsequent PGC specification.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Respuela, PatriciaUNSPECIFIEDorcid.org/0000-0002-9719-7860UNSPECIFIED
Nikolic, MilosUNSPECIFIEDorcid.org/0000-0003-0029-7601UNSPECIFIED
Tan, MinjiaUNSPECIFIEDorcid.org/0000-0002-6784-9653UNSPECIFIED
Frommolt, PeterUNSPECIFIEDorcid.org/0000-0002-1966-8014UNSPECIFIED
Zhao, YingmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wysocka, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDorcid.org/0000-0001-7137-1341UNSPECIFIED
URN: urn:nbn:de:hbz:38-287579
DOI: 10.1016/j.stem.2015.09.010
Journal or Publication Title: Cell Stem Cell
Volume: 18
Number: 1
Page Range: S. 118 - 134
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1875-9777
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA METHYLATION; CELL SPECIFICATION; SELF-RENEWAL; STEM-CELLS; TRANSCRIPTION FACTORS; CHROMATIN; DYNAMICS; TARGETS; LSD1; GENERATIONMultiple languages
Cell & Tissue Engineering; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28757

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