MORPHOLOGICAL AND ELECTROPHYSIOLOGICAL CHARACTERISATION OF HUMAN STEM CELL-DERIVED NEURON

Abstract

Discovery of the ability to reverse a terminally differentiated cell into a pluripotent stem cell state created new opportunities for modeling complex human neurological diseases. However, the iPSC system is greatly heterogeneous and carries problems such as genomic instabilities which complicate the interpretation of phenotypes observed during disease modeling. In this study, we adopted the method for rapid in vitro generation of functional human embryonic stem cell (hESC)-derived neurons with ectopic expression of NGN2, which is less cumbersome and involves less human-to-human variation, to understand the extent of variability between age-matched neurons and the functional profile of hESC-derived neurons with age in vitro. With the help of an unsupervised clustering method, we supplemented the conventional bias prone morphological and electrophysiological categorization of neurons with an unbiased visualization of the variations present. A deeper understanding of the characteristics of hESC-derived neurons is important for their effective use in research and therapeutics.