Leveraging Patient-derived Induced Pluripotent Stem Cells to Understand Cellular Stress Responses Along Neurodevelopment
Neurodevelopment is a highly complex process, sensitive to various cellular stressors that can significantly impact the development and function of the nervous system. By preserving the genetic material of the donor, induced pluripotent stem cells (iPSCs) offer a unique model to investigate how cellular stress impacts neurodevelopment. One way to model cellular stress is through heat stress, a well-characterized method for activating the heat shock response (HSR). Although the HSR has been well-studied in various models, it has not been thoroughly characterized in iPSCs, and how it changes along neurodevelopment is not well known. Here, we investigate the HSR in iPSCs and how it is altered along neurodevelopment. We first measured the expression of HSF1, the master regulator of the HSR and the two main molecular chaperones HSP70 and HSP90. After heat stress, HSP70 expression increased as predicted though HSP90 expression decreased and HSF1 remained unchanged. To further assess the HSR, we used immunostaining to analyze HSF1 activity. When active, HSF1 translocates into the nucleus, and localizes into small punctate structures. We found that HSF1 puncta formation increased following heat stress, confirming high HSF1 activity in iPSCs. Though our results demonstrate an adequate response to heat stress in iPSCs, our preliminary data suggests that neural progenitor cells may exhibit a more robust HSR response compared to iPSCs or neurons. With additional data, these studies will lead to a more comprehensive understanding of the HSR and establish a foundation for discerning how alterations in neurodevelopment may lead to neurological and neurodevelopmental disorders.