Cultured human embryonic stem cells (ESCs) already have some idea of what they want to be when they grow up whereas cultured mouse ESCs are completely undecided about their future careers. A study published in Nature challenges this distinction and shows that some hESCs in culture still haven’t quite made up their minds.
Mouse ESCs are the pinnacle of pluripotency: they have low levels of DNA methylation, express two active X chromosomes (well female cells at least) and resemble closely embryonic cells before implantation. That means that they can produce any cell type of the adult organism. Human ESCs however look more like embryonic cells after implantation, and already express differentiation markers. Stem cell researchers refer to these two states as ‘naïve’ and ‘primed’ pluripotency, respectively.
Several teams have strived to isolate ‘naïve’ human ESCs. Researchers have coerced primed ESCs into naïve cells by expressing transcription factors (TFs) or changing culture conditions. However, it appears that some naïve-like cells were present in cultures of hESCs already, right under their noses.
A team co-led by Yamanaka recently reported that the expression of a particular type of human endogenous retrovirus, HERV-H, is essential for reprogramming.
Unknown to them at the time, researchers in Germany and the UK were finalizing their findings showing that HERV-H expression characterizes naïve hESCs.
Here are some of our favourite highlights:
- Only 4% of cultured hESCs express high levels of HERV-H.
- The expression profile of these cells resembles that of the human ICM and both X chromosomes are active.
- LBP9 is the master switch that regulates HERV-H expression.
- Depletion of LBP9 or HERV-H in hESCs results in loss of self-renewal and affects a similar set of genes.
LBP9 also plays an important role in naïve pluripotency in mice. Yet, HERV-Hs are specific to primates. Thus, the same factor appears to keep cells open to all career choices by a markedly different method of persuasion.
For your career counseling check out Nature, October 2014.