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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 17, 2014 |
| Title |
Lsd1 coordinates trophoblast development by retaining stem cells in their niche and directing cell fate |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Stem cells reside in specific niches providing stemness-maintaining environments. Thus, the regulated migration from these niches is associated with differentiation onset. However, mechanisms retaining stem cells in their niche remain poorly understood. Here, we show that the epigenetic regulator lysine-specific demethylase 1 (Lsd1) organises the trophoblast niche of the early mouse embryo by coordinating migration and invasion of trophoblast stem cells (TSCs). Lsd1 deficiency leads to the depletion of the stem cell pool resulting from precocious migration of TSCs.
Migration is induced by premature expression of the transcription factor Ovol2 that is repressed by Lsd1 in undifferentiated wild-type TSCs. Increasing Ovol2 levels suffices to recapitulate the migration phenotype. Furthermore, Lsd1-deficient TSCs exhibit a developmental bias towards cells of the syncytiotrophoblast and impaired spongiotrophoblast and trophoblast giant cell differentiation. In summary, we describe that the epigenetic modifier Lsd1 coordinates placental development by retaining TSCs in their niche and directing trophoblast differentiation.
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| Overall design |
Mouse trophoblast stem cells (TSCs) were isoloated from a single conditional Lsd1-deficient mouse (Lsd1tm1Schüle). Deletion of Lsd1 was induced eight days before the collection of RNA by addition of 0.2 µM 4OH-tamoxife. Cells were isolated at successive stages of differentiation for total RNA extraction and hybridization on Affymetrix microarrays. To that end, we harvested cells at three time-points: before induction of differentiation (d0), two days after induction of differentiation (d2), and four days after induction of differentiation (d4). Three replicates (1, 2, 3) for control (-) and Lsd1-deficeint (+) cells were included for each differentiation stage.
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| Contributor(s) |
Hölz S, Günther T, Schüle R |
| Citation(s) |
24448552 |
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| Submission date |
May 25, 2012 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Thomas Günther |
| E-mail(s) |
thomas.guenther@uniklinik-freiburg.de
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| URL |
http://www.uniklinik-freiburg.de/molgyn/live/Persons-1/TG_en.html
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| Organization name |
Freiburg University Medical Center
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| Department |
Central Clinical Research
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| Street address |
Breisacherstr. 66
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| City |
Freiburg |
| ZIP/Postal code |
79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (18)
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| GSM937914 |
wild-type TSCs at d0, biological rep1 |
| GSM937915 |
wild-type TSCs at d0, biological rep2 |
| GSM937916 |
wild-type TSCs at d0, biological rep3 |
| GSM937917 |
KO TSCs at d0, biological rep1 |
| GSM937918 |
KO TSCs at d0, biological rep2 |
| GSM937919 |
KO TSCs at d0, biological rep3 |
| GSM937920 |
wild-type TSCs at d2, biological rep1 |
| GSM937921 |
wild-type TSCs at d2, biological rep2 |
| GSM937922 |
wild-type TSCs at d2, biological rep3 |
| GSM937923 |
KO TSCs at d2, biological rep1 |
| GSM937924 |
KO TSCs at d2, biological rep2 |
| GSM937925 |
KO TSCs at d2, biological rep3 |
| GSM937926 |
wild-type TSCs at d4, biological rep1 |
| GSM937927 |
wild-type TSCs at d4, biological rep2 |
| GSM937928 |
wild-type TSCs at d4, biological rep3 |
| GSM937929 |
KO TSCs at d4, biological rep1 |
| GSM937930 |
KO TSCs at d4, biological rep2 |
| GSM937931 |
KO TSCs at d4, biological rep3 |
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| Relations |
| BioProject |
PRJNA167507 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38277_RAW.tar |
66.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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