Searching for naïve human pluripotent stem cells.
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.
Simone Aparecida Siqueira Fonseca, Roberta Montero Costas, Lygia Veiga Pereira, National Laboratory of Embryonic Stem Cell, Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo 05508-090, Brazil.
Simone Aparecida Siqueira
SA
Fonseca
Simone Aparecida Siqueira Fonseca, Roberta Montero Costas, Lygia Veiga Pereira, National Laboratory of Embryonic Stem Cell, Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo 05508-090, Brazil.
Roberta Montero
RM
Costas
Simone Aparecida Siqueira Fonseca, Roberta Montero Costas, Lygia Veiga Pereira, National Laboratory of Embryonic Stem Cell, Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo 05508-090, Brazil.
Lygia Veiga
LV
Pereira
Epiblast stem cells; Human embryonic stem cells; Naïve pluripotent stem cells; X chromosome inactivation