The transition from local to global patterns governs the differentiation of mouse blastocysts

  • 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.
Author:Sabine C. FischerORCiD, Elena Corujo-Simon, Joaquin Lilao-Garzon, Ernst H. K. StelzerORCiDGND, Silvia Muñoz-DescalzoORCiD
Pubmed Id:
Parent Title (English):PLoS one
Place of publication:Lawrence, Kan.
Contributor(s):Gregory M. Kelly
Document Type:Article
Year of Completion:2020
Date of first Publication:2020/05/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/05/18
Tag:BMP signaling; Blastocysts; Cell differentiation; Embryos; Mathematical models; Notch signaling; Signal inhibition; Stem cells
Issue:(5): e0233030
Page Number:29
First Page:1
Last Page:29
Copyright: © 2020 Fischer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Biowissenschaften / Biowissenschaften
Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
5 Naturwissenschaften und Mathematik / 59 Tiere (Zoologie) / 590 Tiere (Zoologie)
Licence (German):License LogoCreative Commons - Namensnennung 4.0