A GC-centered view of 3D genome organization.

In the past two decades, our understanding of how the genome of mammalian cells is spatially organized in the three-dimensional (3D) space of the nucleus and how key nuclear processes are orchestrated in this space has drastically expanded. While genome organization has been extensively studied at the nanoscale, the higher-order arrangement of individual portions of the genome with respect to their intranuclear as well as reciprocal placement is less thoroughly characterized. Emerging evidence points to the existence of a complex radial arrangement of chromatin in the nucleus. However, what shapes this radial organization and whether it has any functional implications remain elusive. In this mini review, we first summarize our current knowledge on this rather overlooked aspect of mammalian genome organization. We then present a theoretical framework for explaining how the genome might be radially organized, focusing on the role of the guanine and cytosine density along the linear genome. Last, we discuss outstanding questions, hoping to inspire future experiments and spark interest in this topic within the 3D genome community.

Single transcription factor reprogramming of hair follicle dermal papilla cells to induced pluripotent stem cells.

Reprogramming patient-specific somatic cells into induced pluripotent stem (iPS) cells has great potential to develop feasible regenerative therapies. However, several issues need to be resolved such as ease, efficiency, and safety of generation of iPS cells. Many different cell types have been reprogrammed, most conveniently even peripheral blood mononuclear cells. However, they typically require the enforced expression of several transcription factors, posing mutagenesis risks as exogenous genetic material. To reduce this risk, iPS cells were previously generated with Oct4 alone from rather inaccessible neural stem cells that endogenously express the remaining reprogramming factors and very recently from fibroblasts with Oct4 alone in combination with additional small molecules. Here, we exploit that dermal papilla (DP) cells from hair follicles in the skin express all but one reprogramming factors to show that these accessible cells can be reprogrammed into iPS cells with the single transcription factor Oct4 and without further manipulation. Reprogramming was already achieved after 3 weeks and with efficiencies similar to other cell types reprogrammed with four factors. Dermal papilla-derived iPS cells are comparable to embryonic stem cells with respect to morphology, gene expression, and pluripotency. We conclude that DP cells may represent a preferred cell type for reprogramming accessible cells with less manipulation and for ultimately establishing safe conditions in the future by replacing Oct4 with small molecules.