A team of researchers at The University of Texas M. D. Anderson Cancer Center, led by an Indian origin scientist, has discovered that a protein called REST blocks the expression of a microRNA that prevents embryonic stem cells from reproducing themselves, and causes them to differentiate into specific cell types.
Dr. Sadhan Majumder, a professor in M. D. Anderson's Department of Cancer Genetics, says that RE1-silencing transcription factor (REST) plays a dual role in embryonic stem cells.
"It maintains self-renewal, or the cell's ability to make more and more cells of its own type, and it maintains pluripotency, meaning that the cells have the potential to become any type of cell in the body," Nature magazine quoted him as saying.
Embryonic stem cells are known for their unique ability to develop from identical, unspecialised cells, and then differentiate into distinct types of cells with special functions.
Scientists have so far been able to induce embryonic stem cells to develop into heart muscle cells or insulin-producing cells of the pancreas, and hope to use them to restore or replace failing cells in the human body and perhaps treat a wide range of diseases one day.
"Embryonic stem cells have a very high potential in medicine. The critical thing is to learn the mechanisms that could be used to generate a lot of self-renewing embryonic stem cells and be able to differentiate them into various cell types," Majumder said.
During the course of study, the researchers found that REST disarms a specific microRNA called microRNA-21 (miR-21) — which suppresses embryonic stem cells' self-renewal, and is associated with a corresponding loss of expression of critical self-renewal regulators like Oct4, Nanog, Sox2 and c-Myc.
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 say that REST expression was significantly higher in the self-renewal state. According to them, 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.
When the researchers added REST to differentiating cells, it maintained their self-renewal.
The study also revealed that REST is bound to the gene chromatin of a set of microRNAs with the potential to target self-renewal genes. The researchers say that REST controls transcription of 11 microRNAs.
In an earlier research, Majumder's team had shown that about half of medulloblastomas, an aggressive type of children's brain tumour, overexpress REST, which is not found in most neural cells.
"We found that REST is a critical factor in this group of children's brain tumours," 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 scientists are now exploring whether microRNAs might also play a role in medulloblastomas.
"Just as blocking REST function has therapeutic potential in medulloblastoma, blocking REST function to allow for differentiation of embryonic stem cells is a potentially critical step in regenerative medicine," Majumder said.