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| Status |
Public on Mar 01, 2016 |
| Title |
Co-expression networks in generation of induced pluripotent stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We developed an adenoviral vector, in which Yamanaka’s four reprogramming factors (RFs) were controlled by individual CMV promoters in a single cassette (Ad-GFP-SOcMK). This permitted coordinated expression of RFs (SOX2, OCT3/4, c-MYC and KLF4) in a cell for a transient period of time, synchronizing the reprogramming process with the majority of transduced cells assuming induced pluripotent stem cell (iPSC)-like characteristics as early as 3 days. These reprogrammed cells resembled human ES cells with regard to morphology, biomarker expression, and could be differentiated into cells of the germ layers in vitro and in vivo. These iPSC-like cells, however, failed to expand into larger iPSC colonies. The short and synchronized reprogramming process allowed us to study global transcription changes within short time intervals. Weighted Gene Co-Expression Network analysis (WGCNA) identified sixteen large gene co-expression modules, each including members of gene ontology categories involved in cell differentiation and development. In particular, the brown module contained a significant number of ES cell marker genes, whereas the turquoise module contained cell-cycle related genes that were downregulated in contrast to upregulation in human ESCs. Strong coordinated expression of all 4 RFs via adenoviral transduction may constrain stochastic processes and lead to silencing of genes important for cellular proliferation.
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| Overall design |
Cells were dedifferentiated and gene expression assessed at 13 timepoints
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| Contributor(s) |
Paul S, Pflieger L, Dansithong W, Gao F, Coppola G, Pulst S |
| Citation(s) |
26892236 |
| Submission date |
Sep 02, 2015 |
| Last update date |
Nov 27, 2018 |
| Contact name |
Giovanni Coppola |
| E-mail(s) |
gcoppola@ucla.edu
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| Phone |
310-794-4172
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| Organization name |
UCLA
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| Department |
Psychiatry and Neurology
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| Lab |
Neurogenetics
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| Street address |
1524 Gonda, 695 Charles Young Drive South
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA294632 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72676_RAW.tar |
200.6 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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