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| Status |
Public on Oct 29, 2013 |
| Title |
Derivation of novel human ground state naïve pluripotent stem cells [gene expression array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| 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.
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| Overall design |
Total of 12 samples of naïve and primed human ESC lines were analyzed for gene expression. Many of the lines analyzed are genetically matched (H9, WIBR3).
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| Contributor(s) |
Novershtern N, Manor YS, Hanna JH |
| Citation(s) |
24172903 |
| Submission date |
May 13, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Yair S Manor |
| Organization name |
Weizmann Institute of Science
|
| Street address |
234 Hertzel st.
|
| City |
Rehovot |
| ZIP/Postal code |
76100 |
| Country |
Israel |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE52824 |
Derivation of novel human ground state naïve pluripotent stem cells. |
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| Relations |
| BioProject |
PRJNA202896 |
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