Challenging the notion that a stem cells’ pluripotent state is not in fact equal for all cells regardless of their origin has been a recent topic of contention and the subject of a number of recent studies, some of which we discussed in our blog.
Now, another study published in Nature this week adds more fuel to the fire. Titled “Deconstructing transcriptional heterogeneity in pluripotent stem cells” and authored by James Collins, Ph.D., at the Wyss Institute and George Daley, M.D., Ph.D., at Boston Children’s Hospital, the study explores different stem cells’ pluripotent states as a result of various perturbations including chemical treatments, culture environments, and genetic knockouts.
The authors studied mouse stem cells via a single cell-analysis approach, and discovered that there is significant heterogeneity within a stem cell population in terms of their dynamic behavior and expression which in turn influences developmental paths these cells end up taking.
While housekeeping and metabolic gene sets showed consistent expression across individual cells, genes involved in signaling pathways and development were found to be considerably more variable. For instance, removing certain mature microRNAs reconfigured stem cells to altered pluripotency states with enhanced self-renewal ability.
These results, pointing to such transcriptional heterogeneity of pluripotent stem cells, highlight the need to draw up a deeper understanding of these transcriptional networks in order to be able to predict the behavior of various pluripotent stem cells.
This paper adds to the deepening well of knowledge about pluripotency, which is increasingly becoming a non-universal cellular state. In the future, this may be uncovered to be merely a state with a pre-determined fate that is suboptimally maintained across populations.