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E-GEOD-44700 - C/EBPα induces highly efficient macrophage transdifferentiation of selected B-lymphoma /leukemia cell lines and impairs their tumorigenicity

Status
Released on 14 March 2013, last updated on 2 June 2014
Organism
Homo sapiens
Samples (28)
Array (1)
Protocols (8)
Description
Earlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B-cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells' tumorigenicity. Likewise, C/EBPα efficiently converted a B- lymphoblastic leukemia cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced to transdifferentiate by C/EBPα into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy to treat B-cell malignancies. Changes in gene expression during transdifferentiation of BLaER1 cells, comparing uninduced (0h) cells with cells treated with E2 for 3h, 6h, 9h, 12h, 18h, 24h, 36h, 48h, 72h, 120h or 168h. Primary human B-cells and macrophages were used as controls. 2 replicates each.
Experiment type
transcription profiling by array 
Contacts
Francesca Rapino <geo@ncbi.nlm.nih.gov>, Eloy F Robles, Eric M Kallin, Jose A Martinez-Climent, Jose A Richter-Larrea, Thomas Graf
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-44700.idf.txt
Sample and data relationshipE-GEOD-44700.sdrf.txt
Raw data (2)E-GEOD-44700.raw.1.zip, E-GEOD-44700.raw.2.zip
Processed data (1)E-GEOD-44700.processed.1.zip
Array designA-GEOD-13607.adf.txt
Links