Method published in Cell could be used to create new mouse models for autoimmune diseases.
Scientists found that fully mature, differentiated B cells can be reprogrammed to an embryonic stem cell like state without the use of an egg.
In previous research, induced pluripotent stem (IPS) cells had been created from fibroblasts, but it was unknown if they were fully differentiated. Mature B cells have a specific part of their DNA cut out as a final maturation step, giving researchers a way to make sure the resulting IPS cells were not from immature cells.
Similar to the process used to create IPS cells from fibroblast cells, the scientists successfully reprogrammed immature B cells into IPS cells by using retroviruses to transfer four genes (Oct4, Sox2, c-Myc, and Klf4) into the cells’ DNA. An additional factor CCAAT/enhancer-binding-protein-a, however, was needed to nudge mature B cells to be reprogrammed into IPS cells.
The IPS cells from both the mature and immature B cells could be used to create mice. The mice grown from the reprogrammed mature B cells were missing the same part of their DNA as the mature B cells, demonstrating that they were reprogrammed from fully differentiated cells.
This work offers the ability of creating new mouse models for autoimmune diseases such as multiple sclerosis and type 1 diabetes, according to the investigators. For example, mature B or T cells specific for glia could be reprogrammed to IPS cells and then used to create mice with an entire immune system primed to only attack the glia cells, thereby creating a mouse model to study multiple sclerosis.
The researcher was performed by investigators at Whitehead Institute for Biomedical Research and MIT. The study will be published in the April 18 issue of Cell.