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Table 1 Overview of pluripotent states and defining characteristics. Although naïve and primed states of pluripotency have been well characterized, there is no clear consensus of the expected characteristics of their intermediate pluripotent states. This table highlights a number of defining characteristics of naïve and primed pluripotent states, and stipulates on the characteristics that intermediate states might encompass. Although a spectrum of intermediate states may exist, here we hypothetically distinguish between two potential intermediate states, ‘Intermediate 1’, the epiblast immediately after implantation and ‘Intermediate 2’ the epiblast at the onset of gastrulation

From: The many faces of Pluripotency: in vitro adaptations of a continuum of in vivo states

Pluripotent state

Corresponding embryonic stage

Gene expression

Epigenetic profile

Functional potential

Naïve - ESCs

E3.5–4.5

Oct4, Sox2, Nanog, Klf4, Stella, Rex1, Gbx2, Tbx3, Pecam, SSEA-1, Alkaline phosphatase

X reactivation. DE-controlled Oct4 expression.

Pre-imp. Chimaeras. Poor PGCLC generation.

Primed - EpiSCs

E7.25–8.0

Oct4, Sox2, Nanog, SSEA-1, Fgf5, Oct6, Otx2, Brachyury, FoxA2, Sox17, Gata4, Gata6

X inactivation. PE-controlled Oct4 expression.

Post-imp. Chimaeras. Poor PGCLC generation.

Intermediate 1

E5.0–6.25

Oct4, Sox2, low Nanog, SSEA-1, Fgf5, Oct6, Otx2 (no PS or lineage markers)

X reactivation, Equal Oct4 regulation by DE and PE?

Pre and post-imp. Chimaeras.

Efficient PGCLC generation.

Intermediate 2

E6.25–7.25

Early PS/mesoderm markers e.g. Nanog, Brachyury.

No endoderm markers.

X inactivation.

Post-imp. Chimaeras.

Reduced PGCLC generation.

  1. ESCs embryonic stem cells, EpiSCs epiblast stem cells, E embryonic day, DE distal enhancer, PE proximal enhancer, pre-imp. pre-implantation, post-imp. post-implantation, PGCLC primordial germ cell-like cell, PS primitive streak