|
Status |
Public on May 14, 2015 |
Title |
Loss of immunosuppressive and anti-inflammatory properties in transformed human mesenchymal stem cells |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
We used collection of sequentially mutated BM-hMSCs ranging from wild type (no oncogenic hits) to fully transformed hMSCs (targeted with up six oncogenic mutations)to address whether BM-hMSCs at different stages of a well-characterized oncogenic process (normal, immortalized, transformed) retain immunomodulatory properties in vitro and in vivo. We characterize, for the first time, an oncogenic transformation-associated loss of the immunesuppressive and anti-inflammatory properties by hMSCs and identify candidate immune effectors underlying the loss of immunomodulation in transformed hMSCs.
|
|
|
Overall design |
Wild type BM-hMSCs (MSC-0H-GFP) did not develop tumors, meanwhile hMSCs transformed sequentially transformed with 5 oncogenic lesions (p53 inactivation; Rb inactivation; expression of hTERT; stabilization of c-myc; and expression of oncogenic H-RAS) (MSC-5H-GFP) cells gave rise to undifferentiated sarcomas when inoculated into immunedeficient mice. The tumoral transformation process causes the loss of the immunosuppressive and anti-inflamatory propierties of MSC-5H-GFP cells as compared to those of the wild type MSC-0H-GFP cells. To understand the basis of this loss of immunosuppression in transformed hMSCs, gene expression analysis was performed to create the list of differentially expressed genes between MSC-0H-GFP and MSC-5H-GFP cells. Further analysis of altered signaling pathways and upstream regulators were performed using the Ingenuity Pathway Analysis software.
|
|
|
Contributor(s) |
Rodriguez R, Menendez P, Delgado M, Araúzo-Bravo MJ |
Citation(s) |
25358789 |
Submission date |
Feb 18, 2014 |
Last update date |
Jan 15, 2022 |
Contact name |
Marcos J. Araúzo-Bravo |
E-mail(s) |
mararabra@yahoo.co.uk
|
Phone |
+34 943 00 6108
|
Organization name |
Max Planck Institute for Molecular Biomedicine
|
Department |
Cell and Developmental Biology
|
Lab |
Computational Biology and Bionformatics
|
Street address |
Rogentstrasse
|
City |
Muenster |
ZIP/Postal code |
48149 |
Country |
Germany |
|
|
Platforms (1) |
GPL13607 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Feature Number version) |
|
Samples (4)
|
|
Relations |
BioProject |
PRJNA238542 |