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Derivation of hypermethylated pluripotent embryonic stem cells with high potency
- Source :
- Cell Research
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
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Abstract
- Naive hypomethylated embryonic pluripotent stem cells (ESCs) are developmentally closest to the preimplantation epiblast of blastocysts, with the potential to contribute to all embryonic tissues and the germline, excepting the extra-embryonic tissues in chimeric embryos. By contrast, epiblast stem cells (EpiSCs) resembling postimplantation epiblast are relatively more methylated and show a limited potential for chimerism. Here, for the first time, we reveal advanced pluripotent stem cells (ASCs), which are developmentally beyond the pluripotent cells in the inner cell mass but with higher potency than EpiSCs. Accordingly, a single ASC contributes very efficiently to the fetus, germline, yolk sac and the placental labyrinth in chimeras. Since they are developmentally more advanced, ASCs do not contribute to the trophoblast. ASCs were derived from blastocysts in two steps in a chemically defined medium supplemented with Activin A and basic fibroblast growth factor, followed by culturing in ABCL medium containing ActA, BMP4, CHIR99021 and leukemia inhibitory factor. Notably, ASCs exhibit a distinct transcriptome with the expression of both naive pluripotency genes, as well as mesodermal somatic genes; Eomes, Eras, Tdgf1, Evx1, hand1, Wnt5a and distinct repetitive elements. Conversion of established ESCs to ASCs is also achievable. Importantly, ASCs exhibit a stable hypermethylated epigenome and mostly intact imprints as compared to the hypomethylated inner cell mass of blastocysts and naive ESCs. Properties of ASCs suggest that they represent cells at an intermediate cellular state between the naive and primed states of pluripotency.
- Subjects :
- 0301 basic medicine
blastocysts
hypermethylated epigenome
animal structures
placenta
Somatic cell
Germ layer
Biology
Oncogene Protein p21(ras)
Wnt-5a Protein
03 medical and health sciences
Mice
Basic Helix-Loop-Helix Transcription Factors
Inner cell mass
Animals
chimeras
Induced pluripotent stem cell
Molecular Biology
reproductive and urinary physiology
Homeodomain Proteins
yolk sac
Membrane Glycoproteins
Epidermal Growth Factor
Chimera
Sequence Analysis, RNA
Mouse Embryonic Stem Cells
Cell Biology
DNA Methylation
pluripotency
Molecular biology
Embryonic stem cell
Cell biology
Neoplasm Proteins
Mice, Inbred C57BL
030104 developmental biology
Epiblast
ESCs
embryonic structures
Original Article
Stem cell
T-Box Domain Proteins
Leukemia inhibitory factor
Germ Layers
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Cell Research
- Accession number :
- edsair.doi.dedup.....82d3633be2eee4c911f12b7d14e11d6d
- Full Text :
- https://doi.org/10.17863/cam.20672