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27.10.17 Surani lab and colleagues derive 'advanced' pluripotent stem cells

last modified Nov 18, 2017 12:58 PM
In this Cell Research paper the Surani lab describe cells, derived from blastocysts, that exhibit an intermediate potency state between pre- and post-implantation stem cells
27.10.17 Surani lab and colleagues derive 'advanced' pluripotent stem cells

Fig 3B (excerpt): RNA-seq analysis of ASCs indicates they are distinct from ESCs in a developmental progression.

Derivation of hypermethylated pluripotent embryonic stem cells with high potency

Bao S et al. (2017) Cell Res. Oct 27. DOI: 10.1038/cr.2017.134. [Epub ahead of print]

 

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.

 

Read more about research in the Surani lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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