Gastruloid development competence discriminates different states of pluripotency

Cermola, Federica; D'Aniello, Cristina; Tatè, Rosarita; de Cesare, Dario; Martinez Arias, Alfonso; Minchiotti, Gabriella; Patriarca, Eduardo Jorge

doi:http://dx.doi.org/10.1016/j.stemcr.2020.12.013

Gastruloid development competence discriminates different states of pluripotency

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Cermola F, Aniello D'A, Tatè R, Cesare D de, Martinez-Arias A, Minchiotti G et al. Gastruloid development competence discriminates different states of pluripotency. Stem Cell Reports. 2021 Feb 9;16(2):354-369. DOI: 10.1016/j.stemcr.2020.12.013

Abstract

Floating spheroidal aggregates of mouse embryonic stem cells can develop into polarized/elongated organoids, namely gastruloids. We set up a high-performing assay to measure gastruloid formation efficiency (GFE), and found that GFE decreases as pluripotency progresses from naive (GFE ≥ 95%) to primed (GFE = 0) state. Specifically, we show that primed EpiSCs fail to generate proper cell aggregates, while early-primed EpiLCs aggregate but eventually fail to develop into elongated gastruloids. Moreover, we characterized proline-induced cells (PiCs), a LIF-dependent reversible early-primed state of pluripotency, and show that PiCs are able to generate gastruloids (GFE ∼ 50%) and are also competent to differentiate into primordial germ cell-like cells. Thus, we propose the GFE assay as a valuable functional tool to discriminate different states of the pluripotency continuum.