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Title: The transition from local to global patterns governs the differentiation of mouse blastocysts
Authors: Fischer, Sabine C.
Corujo-Simon, Elena
Lilao Garzón, Joaquín 
Stelzer, Ernst H.K.
Muñoz Descalzo, Silvia 
UNESCO Clasification: 32 Ciencias médicas
Keywords: Embrylogy
Transcripction factors
Endoderm, et al
Issue Date: 2020
Journal: PLoS ONE 
Abstract: During mammalian blastocyst development, inner cell mass (ICM) cells differentiate into epiblast (Epi) or primitive endoderm (PrE). These two fates are characterized by the expression of the transcription factors NANOG and GATA6, respectively. Here, we investigate the spatio-temporal distribution of NANOG and GATA6 expressing cells in the ICM of the mouse blastocysts with quantitative three-dimensional single cell-based neighbourhood analyses. We define the cell neighbourhood by local features, which include the expression levels of both fate markers expressed in each cell and its neighbours, and the number of neighbouring cells. We further include the position of a cell relative to the centre of the ICM as a global positional feature. Our analyses reveal a local three-dimensional pattern that is already present in early blastocysts: 1) Cells expressing the highest NANOG levels are surrounded by approximately nine neighbours, while 2) cells expressing GATA6 cluster according to their GATA6 levels. This local pattern evolves into a global pattern in the ICM that starts to emerge in mid blastocysts. We show that FGF/MAPK signalling is involved in the three-dimensional distribution of the cells and, using a mutant background, we further show that the GATA6 neighbourhood is regulated by NANOG. Our quantitative study suggests that the three-dimensional cell neighbourhood plays a role in Epi and PrE precursor specification. Our results highlight the importance of analysing the three-dimensional cell neighbourhood while investigating cell fate decisions during early mouse embryonic development.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0233030
Source: PLoS ONE [EISSN 1932-6203], v. 15 (5), e0233030 (Mayo 2020)
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