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Review
. 2015 Apr 26;7(3):649-56.
doi: 10.4252/wjsc.v7.i3.649.

Searching for naïve human pluripotent stem cells

Simone Aparecida Siqueira Fonseca  1 , Roberta Montero Costas  1 , Lygia Veiga Pereira  1
Affiliations
Review

Searching for naïve human pluripotent stem cells

Simone Aparecida Siqueira Fonseca et al. World J Stem Cells. .

Abstract

Normal mouse pluripotent stem cells were originally derived from the inner cell mass (ICM) of blastocysts and shown to be the in vitro equivalent of those pre-implantation embryonic cells, and thus were called embryonic stem cells (ESCs). More than a decade later, pluripotent cells were isolated from the ICM of human blastocysts. Despite being called human ESCs, these cells differ significantly from mouse ESCs, including different morphology and mechanisms of control of pluripotency, suggesting distinct embryonic origins of ESCs from the two species. Subsequently, mouse pluripotent stem cells were established from the ICM-derived epiblast of post-implantation embryos. These mouse epiblast stem cells (EpiSCs) are morphological and epigenetically more similar to human ESCs. This raised the question of whether cells from the human ICM are in a more advanced differentiation stage than their murine counterpart, or whether the available culture conditions were not adequate to maintain those human cells in their in vivo state, leading to a transition into EpiSC-like cells in vitro. More recently, novel culture conditions allowed the conversion of human ESCs into mouse ESC-like cells called naïve (or ground state) human ESCs, and the derivation of naïve human ESCs from blastocysts. Here we will review the characteristics of each type of pluripotent stem cells, how (and whether) these relate to different stages of embryonic development, and discuss the potential implications of naïve human ESCs in research and therapy.

Keywords: Epiblast stem cells; Human embryonic stem cells; Naïve pluripotent stem cells; X chromosome inactivation.

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Figures

Figure 1
Figure 1
First two cell segregations during preimplatation embryonic development. A: In blue, cells from the inner cell mass (ICM) in the early blastocyst, and white, cells from the trophectoderm; B: At the late blastocyst stage, cells from the ICM segregate into cells from the epiblast (green) and the primitive endoderm (orange).
Figure 2
Figure 2
Maintenance of pluripotency by leukemia inhibitory factor and small molecules. Green arrows indicate activation, red blunted lines indicate inhibition. The pluripotent cell must self-renew without committing to any specific cell type. This may be achieved by promoting self-renewal and inhibiting commitment by LIF; or by small molecules (in italic) which inhibit (1) signaling through the FGF receptor tyrosine kinase, thus inhibiting commitment; and (2) GSK3, promoting self-renewal. Adapted from[33]. LIF: Leukemia inhibitory factor; FGFr: Fibroblast growth factor receptor-specific tyrosine kinase; GSK3: Glycogen synthase kinase 3; MEK: Mitogen-activated protein kinase.
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