Interrogating Adult Neural Stem Cell Plasticity using a Zebrafish Model

Abstract

<p>Stem cells are a promising option for human medical therapy. While pluripotent embryonic stem cells have an almost unlimited differentiation potential to become any type of cell, multipotent adult stem cells have a much more limited ability to differentiate. In order to better understand how adult stem cells choose their fate, two main factors were investigated: intrinsic versus extrinsic influences. This was accomplished by implanting rat adult hippocampal progenitor/stem cells (AHPCs) - which normally differentiate into neurons, astrocytes, and oligodendrocytes - into zebrafish embryos during the blastula stage, an environment with almost unlimited potential for stem cells. These embryos were then allowed to grow to three or five days post-fertilization (dpf), at which point they possess a developed nervous system and are free-swimming. The fish were then imaged using fluorescence microscopy to monitor the fate and localization of the AHPCs in relation to the embryo. The results showed a majority of the AHPCs migrating to the outer eye region (38.5%), central nervous system (26.7%), and superficial skin layer (20.7%). Immunolabeling procedures to identify differentiated cell-types revealed the highest percentage of transplanted AHPCs were TuJ1-labeled (73.4%), which distinguishes immature neurons. No significant difference in AHPC survival between 3 dpf and 5 dpf were found. This preliminary analysis reveals that these brain stem cells are likely influenced by intrinsic cell machinery - regulation of gene expression - than their environment when choosing their fate. Through this knowledge, adult stem cells and their cell regulation behaviors can be further investigated to potentially find similar drug options that may mimic the regulation of their expression.</p>