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World J Stem Cells. Apr 26, 2015; 7(3): 649-656
Published online Apr 26, 2015. doi: 10.4252/wjsc.v7.i3.649
Searching for naïve human pluripotent stem cells
Simone Aparecida Siqueira Fonseca, Roberta Montero Costas, Lygia Veiga Pereira
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
Author contributions: Fonseca SAS, Costas RM and Pereira LV reviewed the literature and wrote the manuscript; Costas RM made the figures; Pereira LV coordinated the work.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico/Departamento de Ciência e Tecnologia do Ministério da Saúde (CNPq/MS/DECIT), Banco Nacional de Desenvolvimento Econômico e Social (BNDES) and Financiadora de Estudos e Projetos (FINEP); the fellowship from CNPq (Costas RM); and a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Fonseca SAS).
Conflict-of-interest: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lygia Veiga Pereira, National Laboratory of Embryonic Stem Cell, Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo 05508-090, Brazil. lpereira@usp.br
Telephone: +55-11-30917476 Fax: +55-11-30917553
Received: November 29, 2014
Peer-review started: November 29, 2014
First decision: December 12, 2014
Revised: December 18, 2014
Accepted: January 18, 2015
Article in press: January 20, 2015
Published online: April 26, 2015
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: Naïve pluripotent stem cells, Epiblast stem cells, X chromosome inactivation, Human embryonic stem cells

Core tip: Mouse embryonic stem cells (ESCs) are the in vitro equivalent of the epiblast of preimplantation embryos. Human ESCs on the other hand, although also pluripotent, appear to be in a more advanced developmental stage than their murine counterpart. Recently, several reports described culture conditions able to support mouse ESC-like human ESCs, called naïve human ESCs. Here we will review the search for human naïve ESCs, discussing their biological and practical relevance.