Instructions for Assembling the Early Mammalian Embryo

White, Martin; Zenker, Jennifer; Bissière, Stéphanie; Plachta, Nicolas

doi:10.1016/j.devcel.2018.05.013

Cited by 86 publications

(88 citation statements)

References 132 publications

(168 reference statements)

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“…10). Polar TE-driven maturation in human is reminiscent of the ICM-polar TE molecular dialog observed in mouse embryoids 17,28 . However, human specific events might be involved as some genes critical for mouse TE maturation are not expressed in human, such as KLF6.…”

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confidence: 96%

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Spatio-temporal analysis of human preimplantation development reveals dynamics of epiblast and trophectoderm

Meistermann

Loubersac

Reignier

et al. 2019

Preprint

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Recent technological advances such as single-cell RNAseq 1-3 and CRISPR-CAS9-mediated knock-out 4 have allowed an unprecedented access into processes orchestrating human preimplantation development 5 . However, the sequence of events which occur during human preimplantation development are still unknown. In particular, timing of first human lineage specification, the process by which the morula cells acquire a specific fate, remains elusive. Here, we present a human preimplantation development model based on transcriptomic pseudotime modelling of scRNAseq biologically validated by spatial information and precise time-lapse staging. In contrast to mouse, we show that trophectoderm (TE) / inner cell mass (ICM) lineage specification in human is only detectable at the transcriptomic level at the blastocyst stage, just prior to expansion. We validated the expression profile of novel markers enabling precise staging of human preimplantation embryos, such as IFI16 which highlights establishment of epiblast (EPI) and NR2F2 which appears at the transition from specified to mature TE. Strikingly, mature TE cells arise from the polar side, just after specification, supporting a model of polar TE cells driving TE

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confidence: 96%

“…Studies in mammalians showed establishment of tight and adherent junctions at the morula stage, sealing the embryo [17][18][19] . Transcriptomic profile of adherent junction gene CDH1 and TJP3 tight junction protein in human are similar to mouse and bovine [17][18][19] (Fig. 2c).…”

mentioning

confidence: 99%

Spatio-temporal analysis of human preimplantation development reveals dynamics of epiblast and trophectoderm

Meistermann

Loubersac

Reignier

et al. 2019

Preprint

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“…The choice of modelling methods used in a computational description of a biological phenomenon depends on the processes that the model describes. One peculiarity of embryonic development is that many processes are simultaneously at play and closely interact with each other (White et al, 2018). The main processes are schematized in Fig.…”

Section: Key Modelling Choicesmentioning

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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“…The first cell-specification event that separates the totipotent cells of the morula into two distinct lineages is evident at this time. The apical blastomeres exposed to the outside ultimately differentiate to form the extraembryonic trophectoderm (TE) while the cells surrounded on all sides by their neighbors remain nonpolar and largely contribute to the pluripotent inner cell mass (ICM) at the blastocyst stage (Chazaud and Yamanaka, 2016;Leung et al, 2016;Rossant, 2018;White et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Glucose metabolism distinguishes TE from ICM fate during mammalian embryogenesis

Chi

Sharpley

Nagaraj

et al. 2019

Preprint

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The mouse embryo undergoes compaction at the 8-cell stage and its transition to 16 cells generates polarity such that the outer apical cells are trophectoderm (TE) precursors and the inner cell mass (ICM) gives rise to the embryo. We report here, that this first cell fate specification event is controlled by glucose metabolism. Glucose does not fuel mitochondrial ATP (energy) generation and glycolysis is dispensable for blastocyst formation. Glucose does not help synthesize amino acids, fatty acids, and nucleobases. Instead, glucose metabolized by the hexosamine biosynthetic pathway (HBP) allows nuclear localization of YAP1, and the pentose phosphate pathway (PPP), along with sphingolipid (S1P) signaling, activates mTOR and allows translation of AP-2γ. YAP1, TEAD4 and AP-2γ physically interact to form a nuclear complex that controls TE-specific gene transcription. Glucose signaling has no role in ICM specification, but this cascade of events constituting "Developmental Metabolism" specifically controls the fate of TE cells. KeywordsDevelopmental metabolism, preimplantation embryo, glucose, trophectoderm, pentose phosphate pathway, hexosamine biosynthetic pathway, YAP1, S1P signaling, AP-2 Trim- Away, morula-blastocystWe would like to thank all members of our laboratory for their suggestions and support.Yonggang Zhou performed RNA seq analysis that was used in this manuscript. We thank Daniel Braas, and Johanna ten Hoeve-Scott at the UCLA Metabolomics Center for their generous help with metabolomics analysis. We appreciate many inputs by Tom Graeber, Heather Christofk and Hilary Coller. Christofk and Coller also helped by providing several antibody reagents. We thank Wei Liao, Qin An, Wanlu Liu and Steve Jacobsen for help with RNA sequencing experiments and bioinformatics analysis of RNA expression data, and Huachun Liu for help with molecular cloning and related molecular analysis. We thank Bin Gu at Sick Kids, Toronto for useful suggestions including for microinjection, and Bin Zhao at Zhejiang University for valuable discussions.

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Instructions for Assembling the Early Mammalian Embryo

Cited by 86 publications

References 132 publications

Spatio-temporal analysis of human preimplantation development reveals dynamics of epiblast and trophectoderm

Spatio-temporal analysis of human preimplantation development reveals dynamics of epiblast and trophectoderm

Computational models for the dynamics of early mouse embryogenesis

Glucose metabolism distinguishes TE from ICM fate during mammalian embryogenesis

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