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  Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells

Zhu, D., Hölz, S., Metzger, E., Pavlovic, M., Jandausch, A., Jilg, C., et al. (2014). Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells. NATURE COMMUNICATIONS, 5: 3174. doi:10.1038/ncomms4174.

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 Creators:
Zhu, Dongmei1, Author
Hölz, Stefanie1, Author
Metzger, Eric1, Author
Pavlovic, Mihael1, Author
Jandausch, Anett1, Author
Jilg, Cordula1, Author
Galgoczy, Petra1, Author
Herz, Corinna1, Author
Moser, Markus2, Author              
Metzger, Daniel1, Author
Günther, Thomas1, Author
Arnold, Sebastian J.1, Author
Schüle, Roland1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: EPITHELIAL-MESENCHYMAL TRANSITION; LARGE GENE LISTS; HISTONE DEMETHYLASE; PLACENTAL DEVELOPMENT; EPIGENETIC LANDSCAPE; ANDROGEN-RECEPTOR; LSD1; TRANSCRIPTION; LINEAGE; TROPHECTODERM
 Abstract: Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. Embryonic parts of the mammalian placenta are generated from differentiating trophoblast stem cells (TSCs) invading the maternal decidua. Here we demonstrate that lysine-specific demethylase 1 (Lsd1) regulates differentiation onset of TSCs. Deletion of Lsd1 in mice results in the reduction of TSC number, diminished formation of trophectoderm tissues and early embryonic lethality. Lsd1-deficient TSCs display features of differentiation initiation, including alterations of cell morphology, and increased migration and invasion. We show that increased TSC motility is mediated by the premature expression of the transcription factor Ovol2 that is directly repressed by Lsd1 in undifferentiated cells. In summary, our data demonstrate that the epigenetic modifier Lsd1 functions as a gatekeeper for the differentiation onset of TSCs, whereby differentiation-associated cell migration is controlled by the transcription factor Ovol2.

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Language(s): eng - English
 Dates: 2014-01
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000331104000011
DOI: 10.1038/ncomms4174
 Degree: -

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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 5 Sequence Number: 3174 Start / End Page: - Identifier: ISSN: 2041-1723