Neural stem cells (NSC) are present in two main regions of the adult central nervous system (CNS), the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus of the hippocampus. These NSC proliferate throughout life, and are able to differentiate into neurons or glial cells. The neural stem cells present in the SVZ express the intermediate filament (IF) glial fibrillary acidic protein (GFAP), typifying them as astrocytes. These neurogenic astrocytes have the exciting potential to replace degenerating neurons in brains of patients suffering from still incurable neurodegenerative disorders.
Tissue Transglutaminase (TG2) is a ubiquitously expressed enzyme that is also present in the human brain. TG2 belongs to the transglutaminase family, which are calcium-dependent enzymes which catalyzes cross-linking or deamidation of proteins. TG2 has been implicated in various physiological processes, including cell adhesion and migration, extracellular matrix formation, apoptosis and cell survival, and cell differentiation.
It has been shown that TG2 is present in mesenchymal stem cells and is essential for integrin mediated adhesion and survival of these cells. Recently, it was published that TG2 can interact with IFs and is thereby involved in cell signalling, resulting in enhanced cell proliferation. These findings, together with the fact that TG2 can be involved in cell differentiation and migration, suggest that TG2 might have an important function in neurogenic astrocytes.
Therefore, we hypothesize that is present in GFAP positive NSC in the SVZ. To study this hypothesis, we will perform immunohistochemical stainings on human SVZ material and determine the presence of TG2 in human SVZ stem cells in vitro. If TG2 is present in these neurogenic astrocytes, we will study the function of TG2 in these cells.
Techniques: performing different methods such as immunohistochemical stainings, cell culture, RNA isolation and qPCR, protein isolation and western-blot.
Duration: min. 6 months
Contact Miriam van Strien to get more information about the project.
tel: 020-5665516
e-mail: m.van.strien@nin.knaw.nl