Three-dimensional cell neighbourhood impacts differentiation in the inner mass cells of the mouse blastocyst

Fischer, Sabine; Corujo-Simon, Elena; Lilao-Garzón, Joaquín; Stelzer, Ernst H. K.; Muñoz-Descalzo, Silvia

doi:10.1101/159301

Cited by 5 publications

(8 citation statements)

References 67 publications

(124 reference statements)

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“…We found that patterning of NANOG and GATA6 at the stage of 24 h ICM organoids appears in clusters of identical fates. Our data for the neighborhood composition in mouse blastocysts together with a previous study ( 19 ) indicate that cell fate clustering is also present in vivo.…”

Section: Discussionsupporting

confidence: 81%

“…7 A ). We used our recently developed multiscale image analysis pipeline that combines automated cell nuclei segmentation with topological and graph analyses ( 18 , 19 ). This pipeline provides more than 30 morphological features and fluorescent intensities of individual nuclei, the cellular neighborhood and the ICM organoid as a whole.…”

Section: Resultsmentioning

confidence: 99%

“…In these three-dimensional cell graphs, pairs of vertices are connected by edges signifying a neighborhood relation between two cell nuclei. Because staging based on geometrical features such as cell number is not appropriate for our comparative analysis, we grouped the blastocysts into three developmental stages based on the progress of their development ( 19 ). Because the proportions of the four cell populations are a strong indicator for the development of mouse embryos, we used this criterion to stage the embryos ( 22 , 30 ).…”

Section: Resultsmentioning

confidence: 99%

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Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering

Mathew

Muñoz-Descalzo

Corujo-Simon

et al. 2019

Biophysical Journal

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During mammalian preimplantation, cells of the inner cell mass (ICM) adopt either an embryonic or an extraembryonic fate. This process is tightly regulated in space and time and has been studied previously in mouse embryos and embryonic stem cell models. Current research suggests that cell fates are arranged in a salt-and-pepper pattern of random cell positioning or a spatially alternating pattern. However, the details of the three-dimensional patterns of cell fate specification have not been investigated in the embryo nor in in vitro systems. We developed ICM organoids as a, to our knowledge, novel three-dimensional in vitro stem cell system to model mechanisms of fate decisions that occur in the ICM. ICM organoids show similarities to the in vivo system that arise regardless of the differences in geometry and total cell number. Inspecting ICM organoids and mouse embryos, we describe a so far unknown local clustering of cells with identical fates in both systems. These findings are based on the three-dimensional quantitative analysis of spatiotemporal patterns of NANOG and GATA6 expression in combination with computational rule-based modeling. The pattern identified by our analysis is distinct from the current view of a salt-and-pepper pattern. Our investigation of the spatial distributions both in vivo and in vitro dissects the contributions of the different parts of the embryo to cell fate specifications. In perspective, our combination of quantitative in vivo and in vitro analyses can be extended to other mammalian organisms and thus creates a powerful approach to study embryogenesis.

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Section: Discussionsupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering

Mathew

Muñoz-Descalzo

Corujo-Simon

et al. 2019

Biophysical Journal

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“…This assumption is known as the polarity-based hypothesis . We also did not consider the important role played by surface contractility ( Maître et al, 2016 ), nor recent results showing the key role played by the cell three-dimensional neighbourhood ( Fischer et al, 2018 ). In the future, physical interactions could be considered in a computational framework similar to that developed for the Epi/PrE specification ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Signalling-modulated gene regulatory networks in early mammalian development

Caluwé

Tosenberger

Gonze

et al. 2019

Journal of Theoretical Biology

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Early mammalian embryo is a paradigm of dynamic, self-organised process. It involves gene expression, cell division and intercellular signalling. How these processes interact to ensure reproducible development is being often investigated by modelling, which allows to dissect the mechanisms controlling cell fate decisions. In this work, we present two models based on ordinary differential equations describing the first and second specification processes in the mouse embryo. Together, they describe the cell fate decisions leading to the first three cell lineages which form the blastocyst 4.5 days after fertilisation: the trophectoderm, the epiblast and the primitive endoderm. Both specifications rely on multistability, and signalling allows the selection of the appropriate steady-state. In addition to the gene regulatory network, the first specification process is indeed controlled by the Hippo pathway, which is itself controlled by cell polarity and cell-to-cell contacts. This leads to a spatially organised arrangement of cells. The second specification process is controlled by Fgf signalling and leads to a salt and pepper distribution of the two cell types. We discuss the respective mechanisms and their physiological implications.

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“…It could refer to a random distribution of Epi and PrE cells, or to a spatial arrangement in which Epi cells are preferentially surrounded by PrE cells and vice-versa (like in a chess-board). This question was recently investigated by Fischer et al, (2017). These authors first performed a quantitative 3D analysis of cell neighbourhood in ~E4.0 mouse embryos.…”

Section: Salt and Pepper Patternmentioning

confidence: 99%

Computational models for the dynamics of early mouse embryogenesis

Tosenberger¹,

Gonze²,

Chazaud³

et al. 2019

Int. J. Dev. Biol.

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Early embryonic development, from the zygote to the blastocyst, is a paradigm of a dynamic, self-organised process. It involves gene expression, mechanical interactions between cells, cell division and inter- and intracellular signalling. Imaging and transcriptomic data have significantly improved our understanding of early embryogenesis in mammals. However, they also reveal a great level of complexity. How the genetic, mechanical, and regulatory processes interact to ensure reproducible development is thus much investigated by computational modelling, which allows a dissection of the mechanisms controlling cell fate decisions. In this review, we discuss the main types of modelling approaches that have been used to investigate the dynamics of preimplantation mammalian development. We also discuss the insights provided by modelling into our understanding of the specification processes leading to the three types of cells in the embryo 4.5 days after fertilization: the trophectoderm, the epiblast and the primitive endoderm.

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Three-dimensional cell neighbourhood impacts differentiation in the inner mass cells of the mouse blastocyst

Cited by 5 publications

References 67 publications

Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering

Mouse ICM Organoids Reveal Three-Dimensional Cell Fate Clustering

Signalling-modulated gene regulatory networks in early mammalian development

Computational models for the dynamics of early mouse embryogenesis

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