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Naive Pluripotent Stem Cells Derived Directly from Isolated Cells of the Human Inner Cell Mass.

Published version
Peer-reviewed

Repository DOI


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Authors

Guo, Ge 
von Meyenn, Ferdinand 
Santos, Fatima 
Chen, Yaoyao 

Abstract

Conventional generation of stem cells from human blastocysts produces a developmentally advanced, or primed, stage of pluripotency. In vitro resetting to a more naive phenotype has been reported. However, whether the reset culture conditions of selective kinase inhibition can enable capture of naive epiblast cells directly from the embryo has not been determined. Here, we show that in these specific conditions individual inner cell mass cells grow into colonies that may then be expanded over multiple passages while retaining a diploid karyotype and naive properties. The cells express hallmark naive pluripotency factors and additionally display features of mitochondrial respiration, global gene expression, and genome-wide hypomethylation distinct from primed cells. They transition through primed pluripotency into somatic lineage differentiation. Collectively these attributes suggest classification as human naive embryonic stem cells. Human counterparts of canonical mouse embryonic stem cells would argue for conservation in the phased progression of pluripotency in mammals.

Description

Keywords

Animals, Blastocyst, Cell Differentiation, Cell Line, Cell Lineage, Cell Proliferation, Cells, Cultured, DNA Methylation, Fluorescent Antibody Technique, Gene Expression Profiling, Germ Layers, Human Embryonic Stem Cells, Humans, Mice, Myocytes, Cardiac, Pluripotent Stem Cells, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

6

Publisher

Elsevier BV
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/M004023/1)
Medical Research Council (MC_PC_12009)
MRC (G1100526)
This work was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation (SNF)/Novartis SNF (F.v.M.) and core funding to the Cambridge Stem Cell Institute from the Wellcome Trust and Medical Research Council. AS is a Medical Research Council Professor.