Coupling between chromosome intermingling and gene regulation during cellular differentiation

- Nuclear morphology was stabilized with increased stiffness during differentiation.
- Size-dependent radial positioning of chromosomes was established during differentiation.
- Transcription-dependent chromosome intermingling is established during differentiation.
- Chromosomes with similar transcription activity tend to be in physical proximity.
- Visualizing nano-scale chromosomal contacts within intermingling regions.

In this article, we summarize current findings for the emergence of biophysical properties such as nuclear stiffness, chromatin compaction, chromosome positioning, and chromosome intermingling during stem cell differentiation, which eventually correlated with the changes of gene expression profiles during cellular differentiation. An overview is first provided to link stem cell differentiation with alterations in nuclear architecture, chromatin compaction, along with nuclear and chromatin dynamics. Further, we highlight the recent biophysical and molecular approaches, imaging methods and computational developments in characterizing transcription-related chromosome organization especially chromosome intermingling and nano-scale chromosomal contacts. Finally, the article ends with an outlook towards the emergence of a functional roadmap in setting up chromosome positioning and intermingling in a cell type specific manner during cellular differentiation.