Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites

2020 ◽  
Author(s):  
Martin Estermann
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Tube ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

Reconstitution of a Patterned Neural Tube from Single Mouse Embryonic Stem Cells

2017 ◽  
pp. 43-55 ◽  
Author(s):  
Keisuke Ishihara ◽  
Adrian Ranga ◽  
Matthias P. Lutolf ◽  
Elly M. Tanaka ◽  
Andrea Meinhardt
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Tube ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells

scholarly journals Folate deficiency induced H2A ubiquitination to lead to downregulated expression of genes involved in neural tube defects

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Pei Pei ◽  
Xiyue cheng ◽  
Juan Yu ◽  
Jinying Shen ◽  
Xue Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Embryonic Stem ◽  
Folate Deficiency ◽  
Mouse Embryonic Stem Cells ◽  
Neural Tube Closure ◽  
Serum Folate ◽  
Tube Closure

Abstract Background Neural tube defects (NTDs) are common congenital malformations resulting in failure of the neural tube closure during early embryonic development. Although it is known that maternal folate deficiency increases the risk of NTDs, the mechanism remains elusive. Results Herein, we report that histone H2A monoubiquitination (H2AK119ub1) plays a role in neural tube closure. We found that the folate antagonist methotrexate induced H2AK119ub1 in mouse embryonic stem cells. We demonstrated that an increase in H2AK119ub1 downregulated expression of the neural tube closure-related genes Cdx2, Nes, Pax6, and Gata4 in mouse embryonic stem cells under folate deficiency conditions. We also determined that the E3 ligase Mdm2 was responsible for the methotrexate-induced increase in H2AK119ub1 and downregulation of neural tube closure-related genes. Surprisingly, we found that Mdm2 is required for MTX-induced H2A ubiquitination and is recruited to the sites of DSB, which is dependent on DNA damage signaling kinase ATM. Furthermore, folic acid supplementation restored H2AK119ub1 binding to neural tube closure-related genes. Downregulation of these genes was also observed in both brain tissue of mouse and human NTD cases, and high levels of H2AK119ub1 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Pearson correlation analysis showed a significant negative correlation between expression of the neural precursor genes and H2AK119ub1. Conclusion Our results indicate that folate deficiency contributes to the onset of NTDs by altering H2AK119ub1 and subsequently affecting expression of neural tube closure-related genes. This may be a potential risk factor for NTDs in response to folate deficiency.

scholarly journals Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites

2020 ◽  
Author(s):  
Jesse V Veenvliet ◽  
Adriano Bolondi ◽  
Helene Kretzmer ◽  
Leah Haut ◽  
Manuela Scholze-Wittler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Tube ◽  
Primordial Germ Cell ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
High Level ◽  
Post Implantation

AbstractPost-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes inaccessible to deep analysis in vivo. Mouse embryonic stem cells (mESCs) can form aggregates reflecting the post-occipital embryo (gastruloids), but lacking proper morphogenesis. Here we show that embedding of aggregates derived from mESCs in an extracellular matrix compound results in Trunk-Like-Structures (TLS) with a high level of organization comprising a neural tube and somites. Comparative single-cell RNA-seq analysis demonstrates that TLS execute gene-regulatory programs in an embryo-like order, and generate primordial germ cell like cells (PGCLCs). TLS lacking Tbx6 form ectopic neural tubes, mirroring the embryonic mutant phenotype. ESC-derived trunk-like structures thus constitute a novel powerful in vitro platform for investigating lineage decisions and morphogenetic processes shaping the post-implantation embryo.One sentence summaryA platform for generating trunk-like-structures with precursors of spinal cord, bone and muscle from stem cells in a dish

scholarly journals Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites

Science ◽  
2020 ◽  
Vol 370 (6522) ◽  
pp. eaba4937 ◽  
Author(s):  
Jesse V. Veenvliet ◽  
Adriano Bolondi ◽  
Helene Kretzmer ◽  
Leah Haut ◽  
Manuela Scholze-Wittler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Tube ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Sequencing Analysis ◽  
Mouse Development ◽  
Somite Formation ◽  
Post Implantation

Post-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes that are inaccessible to deep analysis in vivo. We found that pluripotent mouse embryonic stem cells (mESCs) form aggregates that upon embedding in an extracellular matrix compound induce the formation of highly organized “trunk-like structures” (TLSs) comprising the neural tube and somites. Comparative single-cell RNA sequencing analysis confirmed that this process is highly analogous to mouse development and follows the same stepwise gene-regulatory program. Tbx6 knockout TLSs developed additional neural tubes mirroring the embryonic mutant phenotype, and chemical modulation could induce excess somite formation. TLSs thus reveal an advanced level of self-organization and provide a powerful platform for investigating post-implantation embryogenesis in a dish.

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