Distinct mesoderm migration phenotypes in extra-embryonic and embryonic regions of the early mouse embryo

Saykali, Bechara; Mathiah, Navrita; Nahaboo, Wallis; Racu, Marie-Lucie; Defrance, Matthieu; Migeotte, Isabelle

doi:10.1101/438721

Cited by 11 publications

(19 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among cytoskeletal components, intermediate filaments display the highest tensile strength and toughness, as well as remarkable elasticity, which allow cells to sustain and recover from large deformations (Loschke et al , 2015). As we found high expression of intermediate filament components keratins (Krt or K) 8 and 18 in ExE mesoderm (Saykali et al , 2019), we set up to explore keratin filament organization and function in mesoderm‐derived ExE membranes around gastrulation.…”

Section: Introductionmentioning

confidence: 99%

Keratin filaments mediate the expansion of extra‐embryonic membranes in the post‐gastrulation mouse embryo

et al. 2022

Self Cite

View full text Add to dashboard Cite

Mesoderm arises at gastrulation and contributes to both the mouse embryo proper and its extra‐embryonic membranes. Two‐photon live imaging of embryos bearing a keratin reporter allowed recording filament nucleation and elongation in the extra‐embryonic region. Upon separation of amniotic and exocoelomic cavities, keratin 8 formed apical cables co‐aligned across multiple cells in the amnion, allantois, and blood islands. An influence of substrate rigidity and composition on cell behavior and keratin content was observed in mesoderm explants. Embryos lacking all keratin filaments displayed a deflated extra‐embryonic cavity, a narrow thick amnion, and a short allantois. Single‐cell RNA sequencing of sorted mesoderm cells and micro‐dissected amnion, chorion, and allantois, provided an atlas of transcriptomes with germ layer and regional information. It defined the cytoskeleton and adhesion expression profile of mesoderm‐derived keratin 8‐enriched cells lining the exocoelomic cavity. Those findings indicate a novel role for keratin filaments in the expansion of extra‐embryonic structures and suggest mechanisms of mesoderm adaptation to the environment.

show abstract

Section: Introductionmentioning

confidence: 99%

Keratin filaments mediate the expansion of extra‐embryonic membranes in the post‐gastrulation mouse embryo

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The gene expression profile in soma g1 suggests these cells may be undergoing epithelialmesenchymal transition (Stemmler et al, 2019). In contrast, soma g2 cells in E14 embryos exhibit epithelial features, with hallmark expression of amnion specific genes GATA3, GATA2, TFAP2A, TFAP2C, OVOL1, KRT7/8/18 (Gomes Fernandes et al, 2018;Xiang et al, 2020), as well as cell adhesion-related genes ITGA3, PKP2, PODXL and AHNAK (Saykali et al, 2019). Trajectory analysis confirmed the pseudo-temporal relationship amongst these cells, with soma g1 nascent mesoderm being closer to epiblast cells, while soma g2 diverge from g1 and PGCs (Fig.…”

mentioning

confidence: 99%

Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage

Zhu

Sang²,

Withey

et al. 2020

Preprint

View full text Add to dashboard Cite

SummaryInvestigations on the human germline and programming are challenging due to limited access to embryonic material. However, the pig as a model may provide insight on transcriptional network and epigenetic reprogramming applicable to both species. Here we show that during the pre- and early migratory stages pig primordial germ cells (PGCs) initiate large-scale epigenetic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and potentially base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3, as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, including in vitro gametogenesis.

show abstract

“…Similar to Veres et al, we identified a subcluster within the NKX6-1+ progenitors that expressed cell division markers ( TOP2A , CENPF , AURKB ), indicating that the cells in this cluster were replicating NKX6-1+ progenitors. We also identified primitive cells in the iPSC-PPCs not represented in the Veres et al study including mesendoderm and early definitive endoderm, which expressed markers for early embryonic development ( COL1A1, COL1A2, AFP, and APOA2 ) (Nowotschin et al, 2019; Saykali et al, 2019; Teo et al, 2015) and iPSCs, which expressed the stem cell marker POUF51 and corresponded to the iPSC scRNA-seq sample. These results are consistent with the differentiation protocol used in Veres et al (Veres et al, 2019), generating similar albeit more advanced cell types than the differentiation protocol we used to generate the iPSC-PPCs.…”

Section: Resultsmentioning

confidence: 66%

Regulatory variants active in iPSC-derived pancreatic progenitor cells are associated with Type 2 Diabetes in adults

Nguyen

D’Antonio‐Chronowska²,

Fujita³

et al. 2021

Preprint

View full text Add to dashboard Cite

Pancreatic progenitor cells (PPC) are an early developmental multipotent cell type that give rise to mature endocrine, exocrine, and ductal cells. To investigate the extent to which regulatory variants active in PPC contribute to pancreatic complex traits and disease in the adult, we derived PPC from induced pluripotent stem cells (iPSCs) of nine unrelated individuals and generated single cell profiles of chromatin accessibility (snATAC-seq) and transcriptome (scRNA-seq). While iPSC-PPC differentiation was asynchronous and included cell types from early to late developmental stages, we found that the predominant cell type consisted of NKX6-1+ progenitors. Genetic characterization using snATAC-seq identified 86,261 regulatory variants that either displayed chromatin allelic bias and/or were predicted to affect active transcription factor (TF) binding sites. Integration of these regulatory variants with 380 fine-mapped type 2 diabetes (T2D) risk loci identified regulatory variants in 209 of these loci that are functional in iPSC-PPC, either by affecting transcription factor binding or through association with allelic effects on chromatin accessibility. The PPC active regulatory variants in 65 of these loci showed strong evidence of causally underlying the association with T2D. Our study shows that studying the functional associations of regulatory variation in iPSC-PPC enables the identification and characterization of causal SNPs for adult Type 2 Diabetes.

show abstract

Distinct mesoderm migration phenotypes in extra-embryonic and embryonic regions of the early mouse embryo

Cited by 11 publications

References 62 publications

Keratin filaments mediate the expansion of extra‐embryonic membranes in the post‐gastrulation mouse embryo

Keratin filaments mediate the expansion of extra‐embryonic membranes in the post‐gastrulation mouse embryo

Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage

Regulatory variants active in iPSC-derived pancreatic progenitor cells are associated with Type 2 Diabetes in adults

Contact Info

Product

Resources

About