Chromatin does not fully acquire the properties of post-mortem neurons during iPSCs-to-neurons differentiation.

However, a critical question remains: how accurately do iPSC-derived neurons mimic the molecular and structural intricacies of post-mortem neurons? In this study, we embark on a comprehensive investigation of chromatin architecture in both iPSC-derived and post-mortem neurons.

We collected and uniformly processed the largest collection of publicly available Hi-C datasets for human and mouse neurons, along with our newly generated maps. The thorough analysis on the resulting data reveals that iPSC-derived neurons retain properties of non-differentiated cells and resemble developing stages of neurons rather than fully mature neurons. Our study not only provides a detailed comparison of chromatin architecture between iPSC-derived and post-mortem neurons but also offers the largest dataset of uniformly processed Hi-C data for human and mouse neurons.