Year 4/NCE

   Our project focused 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 studied the surfaces of human neural stem cells and found that inherent electrical properties of the cell membrane can be used to detect fate without the use of labels. Further studies identified cell surface glycosylation as the primary contributor to the electrical properties that delineate stem cell fate. The electrical properties of stem cells of distinct fates are different enough to allow them to be isolated from each other. Based on this, we made new devices to enrich cells that preferentially form the mature cell type astrocytes (astrocyte precursor cells). The new device is faster and gives better cell enrichment than our previous sorting platforms. Enriched astrocyte precursors have more activity in a 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. 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.