Two states of stem cell pluripotency are thought to exist: naive and primed. ‘Naive’ mouse ESCs are devoid of differentiation bias, while human ESCs have already made some fundamental developmental decisions and are typically considered ‘primed.’ Naive stem cells exist at the beginning of blastocyst development.
‘Primed’ stem cells, from the blastocyst stage, are capable of differentiating into all three germ layers, and they are characterized by expression of high levels of de novo DNA methyltransferases.
A new manuscript describes reverting hESCs (human embryonic stem cells) to a naive-like hypomethylated state, which led to the discovery of important methylation-dependent behavior.
Titled Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory, the manuscript is authored by Dr. Amander Clark’s lab at the University of California, Los Angeles.
Capturing naive-like stem cells is a complicated process. Dr. Clark and colleagues discovered that generating such naive-like cells results in loss of methylation sites, leading to cells with potential developmental problems and loss of methylation sites.
For that reason, the authors postulate that the generation of healthiest pluripotent stem cells is in the primed state, rather than naive as previously thought. This is an intriguing finding that sets new paradigms for generating therapeutically beneficial stem cells for regenerative medicine.
The findings were published in the journal Cell Stem Cell, and can be accessed here.