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| Status |
Public on Jan 01, 2015 |
| Title |
Decreased expression of cell proliferation-related genes in clonally derived skin fibroblasts from children with Silver-Russell syndrome is independent of the degree of 11p15 ICR1 hypomethylation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The in-vitro analysis of the hypomethylation of the imprinting control region 1 (ICR1) within the IGF2/H19 locus is challenged by the mosaic distribution of the epimutation in tissues from children with Silver-Russell syndrome (SRS).
For excluding mosaicism, clonal cultures of skin fibroblasts from four children with SRS and three controls were analyzed. Cell proliferation, IGF-II secretion, and expression of IGF2 and H19 were measured. Microarray expression analysis was performed.
Single cell expansion established severely ICR1 hypomethylated clones (SRShypo) and normomethylated clones (SRSnormo) from patients and controls (Cnormo). IGF2 expression was below the detection limit of the qRT-PCR assay, while H19 expression was detectable, without differences between fibroblast clones. Cell count-related IGF-II release was comparable in supernatants of SRShypo and Cnormo. Cell proliferation was diminished in SRShypo compared to Cnormo (p=.035). Microarray analysis revealed gene expression changes in SRS clones predicting a decrease of cell proliferation and a delay of mitosis.
The analysis of severely ICR1 hypomethylated clonal fibroblasts did not reveal any functional differences towards the normomethylated clones with respect to IGF2 and H19 expression. Furthermore, a clear difference to the clones from healthy individuals was not detected except from a lower proliferation rate arisen from impaired cell cycle progression.
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| Overall design |
16 samples: 8 SRShypo, 4 SRSnormo, 4 Cnormo
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| Contributor(s) |
Heckmann D, Binder G |
| Citation(s) |
25657826 |
| |
| Submission date |
Sep 04, 2014 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Doreen Heckmann |
| E-mail(s) |
[email protected]
|
| Organization name |
DKFZ
|
| Street address |
INF280
|
| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA260286 |
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