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Series GSE52617 Query DataSets for GSE52617
Status Public on Nov 28, 2013
Title Derivation of novel human ground state naïve pluripotent stem cells [ChIP-seq; RRBS-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
Summary Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3b signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters.Upon withdrawal of 2i/LIF, naïve mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalency acquisition on lineage regulatory genes. The feasibility for establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in rodent ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation of cross-species chimaeric embryos that underwent organogenesis following microinjection of human naive iPS cells into mouse morulas. Collectively, our findings establish new avenues for regenerative medicine, patient-specific iPS cell disease modelling and the study of early human development in vitro and in vivo.
Overall design Four chromatin marks H3K4me1, H3K4me3, H3K27ac and H3K27me3 were measured in 5 cell lines: C1, WIBR3, LIS2 and WIS2 (naïve and conventional/primed stem cells), and BGO1 (only naïve stem cells). Reduced representation bisulfite sequencing was performed on primed and naïve (expanded in NHSM-WIS medium) human ESCs. For comparison, RRBS was also performed on primed and naïve mouse pluripotent cells.
Contributor(s) Novershtern N, Weinberger L, Chomsky E, Hanna JH
Citation(s) 24172903
Submission date Nov 21, 2013
Last update date May 15, 2019
Contact name Noa Novershtern
Organization name Weizmann Institute of Science
Department Molecular Genetics
Street address Weizmann Institute
City Rehovot
ZIP/Postal code 7610001
Country Israel
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (59)
GSM1272743 H3K4me1 marks of naïve C1 induced stem cells
GSM1272744 H3K4me3 marks of naïve C1 induced stem cells
GSM1272745 H3K27me3 marks of naïve C1 induced stem cells
This SubSeries is part of SuperSeries:
GSE52824 Derivation of novel human ground state naïve pluripotent stem cells.
BioProject PRJNA229486
SRA SRP033238

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Supplementary file Size Download File type/resource
GSE52617_RAW.tar 148.0 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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