Our project focuses on a major unsolved problem in the neural stem cell field, which is how cells respond to cues in the external environment and decide what type of mature cells to form. Interaction of proteins on the cell surface with signals in the transplantation environment can induce stem cells to generate particular types of mature, functional cells. Thus, cell surface proteins are critical for directing transplanted stem cells to form the appropriate types of mature cells to treat injury or disease. A key modification regulating cell surface proteins is glycosylation, which is the addition of sugars onto proteins and has not been well studied in neural stem cells. We hypothesize key players directing cellular decisions are sugar-coated proteins controlling how stem cells respond to extracellular cues.
This year on the project we found that inherent electrical properties of cells in stem cell populations can be used to isolate them from other types of cells. We made new devices that use a novel approach without cell labeling to enrich cells that preferentially form the mature cell type astrocytes (astrocyte precursor cells). The new device is faster and gives better sorting than our previous versions. Enriched astrocyte precursors have more activity in a particular glycosylation pathway that adds highly branched sugars to proteins. We found these sugars are not just markers revealing what type of mature cells will form, but actively direct the emergence of mature cells. Cells pushed to have more of these sugars resist forming mature cells and when they do mature, the types of cells that form shift depending on the available external cues. We analyzed large data sets to identify proteins changed on the cell surface as cells form different types of mature cells. Our goal is to better understand the development of mature cells, particularly astrocytes and neurons, which will improve the use of these cells to treat brain diseases and injuries.