What is Primed Pluripotency?
Primed pluripotency is a state of stem cells that are still pluripotent, meaning they can form any of the three germ layers:
Ectoderm (e.g., brain, skin)
Mesoderm (e.g., heart, blood, muscle)
Endoderm (e.g., gut, liver, lungs)
However, primed cells are not as flexible as naive pluripotent cells.
They are “primed” or ready to begin differentiating, meaning they are closer to becoming specific cell types.
Origin in the Embryo
Primed pluripotent cells exist in the epiblast of the post-implantation embryo, which forms after the embryo attaches to the uterus.
These cells are more developmentally advanced than naive cells (which come from the earlier, pre-implantation embryo).
Laboratory Examples
Mouse Epiblast Stem Cells (EpiSCs):
Derived from post-implantation mouse embryos.
Serve as the mouse model for primed pluripotency.
Human Embryonic Stem Cells (hESCs):
Most hESCs cultured in labs naturally exist in the primed state, unless specially converted to naive.
Molecular and Epigenetic Features
Epigenetic State:
DNA is more methylated, meaning genes are less accessible for activation.
Chromatin (DNA + protein) is more compact, indicating partial gene silencing.
X-Chromosome Inactivation (Females Only):
One of the two X chromosomes is already inactivated, which happens in more differentiated cells.
This is different from naive cells, which have both X chromosomes active.
Transcription Factors:
Express some core pluripotency factors like OCT4, SOX2, NANOG, but at different levels than in naive cells.
Additional factors like OTX2 are often upregulated, which helps push the cells toward differentiation.
Molecular and Epigenetic Features
Epigenetic State:
DNA is more methylated, meaning genes are less accessible for activation.
Chromatin (DNA + protein) is more compact, indicating partial gene silencing.
X-Chromosome Inactivation (Females Only):
One of the two X chromosomes is already inactivated, which happens in more differentiated cells.
This is different from naive cells, which have both X chromosomes active.
Transcription Factors:
Express some core pluripotency factors like OCT4, SOX2, NANOG, but at different levels than in naive cells.
Additional factors like OTX2 are often upregulated, which helps push the cells toward differentiation.
Growth Requirements and Signaling
Primed cells need specific growth factors to survive and stay pluripotent in culture:
FGF2 (Fibroblast Growth Factor 2) – essential for cell survival and proliferation.
Activin A/Nodal signaling – keeps the cells in the pluripotent state.
If these signals are removed, the cells will start differentiating into specific cell types.
Metabolism and Energy Usage
Primed cells rely more on glycolysis for energy (breaking down glucose in the cytoplasm).
Naive cells rely more on oxidative phosphorylation in the mitochondria.
This metabolic shift reflects their transition toward more active, specialized cells.
Behavior in Experiments
Chimera Formation:
When injected into an early embryo, primed cells do not efficiently integrate into the developing organism.
Naive cells, by contrast, can integrate well and form all tissues, even contribute to the germline.
Colony Morphology (in dishes):
Primed cells grow in flat, spread-out colonies.
Naive cells grow in tight, dome-shaped colonies.
Conceptual Analogy
Imagine pluripotency like a student’s academic journey:
Naive pluripotent cell = a student in elementary school with no set path—can become anything.
Primed pluripotent cell = a high school senior who's chosen a general field (like science or arts), but hasn't picked a specific job yet—options are still open, but more limited.
