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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 25, 2009 |
| Title |
Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis (Expression) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Differentiation of mouse embryonic stem cells (mESCs) is accompanied by changes in replication timing. To explore the relationship between replication timing and cell fate transitions, we constructed genome-wide replication-timing profiles of 22 independent mouse cell lines representing 10 stages of early mouse development, and transcription profiles for seven of these stages. Replication profiles were cell-type specific, with 45% of the genome exhibiting significant changes at some point during development that were generally coordinated with changes in transcription. Comparison of early and late epiblast cell culture models revealed a set of lineage-independent early-to-late replication switches completed at a stage equivalent to the post-implantation epiblast, prior to germ layer specification and down-regulation of key pluripotency transcription factors (Oct4/Nanog/Sox2) and coinciding with the emergence of compact chromatin near the nuclear periphery. These changes were conserved in all subsequent lineages and involved a group of irreversibly down-regulated genes, at least some of which were repositioned closer to the nuclear periphery. Importantly, many genomic regions of partially reprogrammed induced pluripotent stem cells (piPSCs) failed to re-establish ESC-specific replication timing and transcription programs. These regions were enriched for lineage-independent early-to-late changes, which in female cells included the inactive X-chromosome. Taken together, we demonstrate that replication-timing changes are extensive during development. Moreover, a distinct set of lineage-independent, early-to-late changes completed in and stably maintained after the post-implantation epiblast stage is difficult to reprogram and therefore coincides with an epigenetic commitment to differentiation prior to germ layer specification.
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| Overall design |
8 cell lines, with a total of 14 individual replicates (i.e. 6 in duplicates, 2 in single replicates)
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| Contributor(s) |
Hiratani I, Ryba T |
| Citation(s) |
19952138 |
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| Submission date |
Sep 04, 2009 |
| Last update date |
Apr 16, 2013 |
| Contact name |
David M. Gilbert |
| E-mail(s) |
gilbert@bio.fsu.edu
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| Phone |
8506457583
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| Organization name |
Florida State University
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| Street address |
319 Stadium Drive
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| City |
Tallahassee |
| State/province |
Florida |
| ZIP/Postal code |
32306-4295 |
| Country |
USA |
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| Platforms (1) |
| GPL9154 |
NimbleGen Mouse 60-mer Expression Array 42.5K |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE18019 |
Genome-Wide Dynamics of Replication Timing Revealed by In Vitro Models of Mouse Embryogenesis |
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| Relations |
| BioProject |
PRJNA123569 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE17980_RAW.tar |
115.2 Mb |
(http)(custom) |
TAR (of PAIR) |
| Processed data included within Sample table |
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