Comparative computational analysis of pluripotency in human and mouse stem cells

Abstract

Pluripotent cells can be subdivided into two distinct states, the naive and the primed state, the latter being further advanced on the path of differentiation. There are substantial differences in the regulation of pluripotency between human and mouse, and in humans only stem cells that resemble the primed state in mouse are readily available. Reprogramming of human stem cells into a more naive-like state is an important research focus. Here, we developed a pipeline to reanalyze transcriptomics data sets that describe both states, naive and primed pluripotency, in human and mouse. The pipeline consists of identifying regulated start-ups/shut-downs in terms of molecular interactions, followed by functional annotation of the genes involved and aggregation of results across conditions, yielding sets of mechanisms that are consistently regulated in transitions towards similar states of pluripotency. Our results suggest that one published protocol for naive human cells gave rise to human cells that indeed share putative mechanisms with the prototypical naive mouse pluripotent cells, such as DNA damage response and histone acetylation. However, cellular response and differentiation-related mechanisms are similar between the naive human state and the primed mouse state, so the naive human state did not fully reflect the naive mouse state.