Genomic Rewiring of SOX2 Chromatin Interaction Network during Differentiation of ESCs to Postmitotic Neurons.

Cellular differentiation requires dramatic changes in chromatin organization, transcriptional regulation, and protein production. To understand the regulatory connections between these processes, we generated proteomic, transcriptomic, and chromatin accessibility data during differentiation of mouse embryonic stem cells (ESCs) into postmitotic neurons and found extensive associations between different molecular layers within and across differentiation time points. We observed that SOX2, as a regulator of pluripotency and neuronal genes, redistributes from pluripotency enhancers to neuronal promoters during differentiation, likely driven by changes in its protein interaction network. We identified ATRX as a major SOX2 partner in neurons, whose co-localization correlated with an increase in active enhancer marks and increased expression of nearby genes, which we experimentally confirmed for three loci. Collectively, our data provide key insights into the regulatory transformation of SOX2 during neuronal differentiation, and we highlight the significance of multi-omic approaches in understanding gene regulation in complex systems.

Advances in stem cell proteomics.

Stem cells are at the basis of organismal development, characterized by their potential to differentiate towards specific lineages upon receiving proper signals. To understand the molecular principles underlying gain and loss of pluripotency, proteomics plays an increasingly important role owing to technical developments in mass spectrometry and implementation of innovative biochemical approaches. Here we review how quantitative proteomics has been used to investigate protein expression, localization, interaction and modification in stem cells both in vitro and in vivo, thereby complementing other omics approaches to study fundamental properties of stem cell plasticity.