The team found that MiR-21 suppresses embryonic stem cell self-renewal and is associated with a corresponding loss of expression of critical self-renewal regulators, such as Oct4, Nanog, Sox2 and c-Myc. REST counters this by suppressing miR-21 to preserve the cells self-renewal and pluripotency.
The researchers discovered the roles of REST and miR-21 in a series of experiments using cultured mouse embryonic stem cells in either a self-renewal state or a differentiating state. They found that REST expression was significantly higher in the self-renewal state. Withdrawing REST reduced the stem cells ability to reproduce themselves and started differentiation even when the cells were grown under conditions conducive to self-renewal. Adding REST to differentiating cells maintained their self-renewal.
These experiments also revealed that REST is bound to the gene chromatin of a set of microRNAs with the potential to target self-renewal genes. REST controls transcription of 11 microRNAs.
REST Implicated in Pediatric Brain Cancer
Previous laboratory research suggests that the qualities that make REST beneficial in stem cell production and pluripotency may contribute to the development of medulloblastoma, an aggressive type of childrens brain tumor. Medulloblastomas are believed to develop from undifferentiated neural stem cells in the external granule layer of the cerebellum.
In earlier research, Majumders group at M. D. Anderson discovered that about half of these tumors overexpress REST, which is not found in most neural cells. "We found that REST is a critical factor in this group of childrens brain tumors," Majumder said, "and that its major function is to keep a group of specific brain stem cells, or progenitor cells, in a state of stemness."
The researchers hypothesize that by maint
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center