A non-cell autonomous mechanism, based on a minimal number of four inner-cell contacts in the Inner Cell Mass (ICM) of the mouse embryo at E(mbryonic day)3.25 activates the pluripotency master regulator Oct4 and establishes in vivo a very early naïve pluripotent state.

Research, led by Dr. Marcos J. Araúzo Bravo from the Computational Biology and Systems Biomedicine Research Group of the IIS Biodonostia, has just been published online in the open access journal Scientific Reports, belonging to the prestigious publication group Nature, in an article whose first author is Dr. Daniela Gerovska.

The article revisits the study of the 32- to 64-cell mouse embryo transition during the embryonic day E3.25, associated traditionally in literature with the search for an early onset of the second cell-fate decision, the specification of the Inner Cell Mass (ICM) to primitive endoderm and epiblast.

The objective has been to discover new events of very early embryonic decisions that have remained elusive till now for the traditional techniques. For this purpose, the authors designed a new clustering algorithm: Hierarchical Optimal k-Means clustering (HOkM), and applied it on single-cell microarray transcriptomics data from E3.25.

Thanks to this new algorithm they discovered two new subpopulations of ICM cells: the subpopulation from embryos with less than 34 cells (E3.25-LNCs), and the subpopulation from embryos with more than 33 cells (E3.25-HNCs), corresponding to two different developmental stages.

Analyzing the differently expressed genes between the E3.25-LNCs and E3.25-HNCs subpopulations, they found that the expression of Oct4, pluripotency master regulator, is unstable in the subpopulation E3.25-LNC, and stabilizes at high level in the E3.25-HNC subpopulation, with Basigin highly expressed and the chromatin remodeling program initialized to establish a very early naïve pluripotent state in the E3.25-HNCs. The authors hypothesized the existence of a non-cell autonomous mechanism, based on the requirement for at least four inner-cell contacts in a 6-cell kernel in the ICM of embryos with more than 33 cells, which activates Oct4 in the mouse preimplantation embryo.

Computational analysis of single-cell transcriptomics data elucidates the stabilization of Oct4 expression in the E3.25 mouse preimplantation embryo. Daniela Gerovska & Marcos J. Araúzo-Bravo. Scientific Reports.

The paper is freely available online at: www.nature.com/articles/s41598-019-45438-y