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Chemical Cocktail Creates Extended Pluripotent Stem Cells



Review of “Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency” from Cell by Stuart P. Atkinson

In the stem cell world, pluripotent stem cells (PSCs) reign supreme, carrying with them the capacity to differentiate into all the various cell types of an adult organism. However, for the labs of Huan Shen, Juan Carlos Izpisua Belmonte, and Hongkui Deng this capacity was just not enough!

Their new Cell study now describes a chemical cocktail that grant mouse and human PSCs the added ability to generate extraembryonic (ExEm) tissues, including the trophoblast lineages that contribute to placental development, as well as embryonic tissues. These cells, which the authors have designated extended pluripotent stem cells (or EPS), may represent a huge step forward in both basic and translational research [1].

To generate EPS cells, the authors employed a small molecule cocktail (LCDM) that they hoped would promote naïve pluripotency in human and mouse PSCs. This ingenious mixture included human Leukemia inhibitory factor (hLIF), a GSK3 inhibitor (CHIR 99021), as well as two novel small molecules ( (S)-(+)-dimethindene maleate [DiM] and minocycline hydrochloride [MiH]), which may function through the inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1) [2] and histamine and muscarinic receptor signaling.

While the team achieved naïve pluripotency using this cocktail, they also noted that LCDM-treated mouse PSCs integrated into embryonic and extra-embryonic tissues during a chimera assay (applied to assess pluripotency [3]) even when using only a single cell. Furthermore, LCDM treated human PSCs exhibited limited interspecies chimeric competency in vivo, suggesting that these cells also displayed extended pluripotency.

Good things generally transpire after enjoying a cocktail, and this exciting new study is no different! As the authors demonstrate the stable long-term culture of extended pluripotent stem cells, they not that we should be able to take advantage of this chemical combination to “open new avenues for basic and translational research.”

To keep up to date with all the new studies into this new extended pluripotent state, stay in touch with the Stem Cells Portal!


  1. Yang Y, Liu B, Xu J, et al. Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency. Cell 2017;169:243-257 e225.
  2. Hassa PO and Hottiger MO. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci 2008;13:3046-3082.
  3. De Los Angeles A, Ferrari F, Xi R, et al. Hallmarks of pluripotency. Nature 2015;525:469-478.