scholarly journals Adhesion and Growth of Neuralized Mouse Embryonic Stem Cells on Parylene-C/SiO2 Substrates

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3174
Author(s):  
Alan F. Murray ◽  
Evangelos Delivopoulos
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Primary Neurons ◽  
Tissue Engineering Scaffolds ◽  
Parylene C ◽  
Unexpected Outcome

Neuronal patterning on microfabricated architectures has developed rapidly over the past few years, together with the emergence of soft biocompatible materials and tissue engineering scaffolds. Previously, we introduced a patterning technique based on serum and the biopolymer parylene-C, achieving highly compliant growth of primary neurons and astrocytes on different geometries. Here, we expanded this technique and illustrated that neuralized cells derived from mouse embryonic stem cells (mESCs) followed stripes of variable widths with conformity equal to or higher than that of primary neurons and astrocytes. Our results indicate the presence of undifferentiated mESCs, which also conformed to the underlying patterns to a high degree. This is an exciting and unexpected outcome, as molecular mechanisms governing cell and ECM protein interactions are different in stem cells and primary cells. Our study enables further investigations into the development and electrophysiology of differentiating patterned neural stem cells.

scholarly journals ETV2/ER71 regulates the generation of FLK1+ cells from mouse embryonic stem cells through miR-126-MAPK signaling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ju Young Kim ◽  
Dong Hun Lee ◽  
Joo Kyung Kim ◽  
Hong Seo Choi ◽  
Bhakti Dwivedi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Embryonic Stem ◽  
Mapk Signaling ◽  
Mouse Embryonic Stem Cells ◽  
Micro Rna ◽  
Mitogen Activated Protein Kinase ◽  
The Novel

AbstractPrevious studies including ours have demonstrated a critical function of the transcription factor ETV2 (ets variant 2; also known as ER71) in determining the fate of cardiovascular lineage development. However, the underlying mechanisms of ETV2 function remain largely unknown. In this study, we demonstrated the novel function of the miR (micro RNA)-126-MAPK (mitogen-activated protein kinase) pathway in ETV2-mediated FLK1 (fetal liver kinase 1; also known as VEGFR2)+ cell generation from the mouse embryonic stem cells (mESCs). By performing a series of experiments including miRNA sequencing and ChIP (chromatin immunoprecipitation)-PCR, we found that miR-126 is directly induced by ETV2. Further, we identified that miR-126 can positively regulate the generation of FLK1+ cells by activating the MAPK pathway through targeting SPRED1 (sprouty-related EVH1 domain containing 1). Further, we showed evidence that JUN/FOS activate the enhancer region of FLK1 through AP1 (activator protein 1) binding sequences. Our findings provide insight into the novel molecular mechanisms of ETV2 function in regulating cardiovascular lineage development from mESCs.

SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc- SMPDL3B

2021 ◽  
Author(s):  
Wei Fan ◽  
Shuang Tang ◽  
Xiaojuan Fan ◽  
Yi Fang ◽  
Xiaojiang Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Sphingolipid Metabolism

AbstractSphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.

scholarly journals Inhibition of β-catenin–TCF1 interaction delays differentiation of mouse embryonic stem cells

2015 ◽  
Vol 211 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Sujash S. Chatterjee ◽  
Abil Saj ◽  
Tenzin Gocha ◽  
Matthew Murphy ◽  
Foster C. Gonsalves ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Protein Interactions ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Protein Protein Interactions ◽  
Nanog Expression ◽  
Context Specific

The ability of mouse embryonic stem cells (mESCs) to self-renew or differentiate into various cell lineages is regulated by signaling pathways and a core pluripotency transcriptional network (PTN) comprising Nanog, Oct4, and Sox2. The Wnt/β-catenin pathway promotes pluripotency by alleviating T cell factor TCF3-mediated repression of the PTN. However, it has remained unclear how β-catenin’s function as a transcriptional activator with TCF1 influences mESC fate. Here, we show that TCF1-mediated transcription is up-regulated in differentiating mESCs and that chemical inhibition of β-catenin/TCF1 interaction improves long-term self-renewal and enhances functional pluripotency. Genetic loss of TCF1 inhibited differentiation by delaying exit from pluripotency and conferred a transcriptional profile strikingly reminiscent of self-renewing mESCs with high Nanog expression. Together, our data suggest that β-catenin’s function in regulating mESCs is highly context specific and that its interaction with TCF1 promotes differentiation, further highlighting the need for understanding how its individual protein–protein interactions drive stem cell fate.

scholarly journals SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc- SMPDL3B

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Wei Fan ◽  
Shuang Tang ◽  
Xiaojuan Fan ◽  
Yi Fang ◽  
Xiaojiang Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neural Differentiation ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Sphingolipid Metabolism

Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.

scholarly journals Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells

2020 ◽  
Author(s):  
Kousuke Uranishi ◽  
Masataka Hirasaki ◽  
Yuka Kitamura ◽  
Yosuke Mizuno ◽  
Masazumi Nishimoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Dna Binding ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Meiotic Entry

SUMMARYMouse embryonic stem cells (ESCs) have high potential for meiotic entry, like germ cells. Although the physiological meaning of this potential is not known, it is certain that a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively, in which MGA has important roles in DNA binding as well as in constructing the complex as a scaffolding component. As a salient feature, MGA bears two distinct DNA-binding domains termed bHLHZ and T-box. However, how these features contribute to the functions of PRC1.6, particularly in the repression of meiotic genes, remains largely obscure. Here, we demonstrated that both DNA binding domains of Mga repress distinct sets of genes in murine ESCs, and substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that both DNA binding domains of Mga, in particular bHLHZ, are crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry in collaboration with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.

scholarly journals Nanog Dynamics in Mouse Embryonic Stem Cells: Results from Systems Biology Approaches

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Lucia Marucci
Keyword(s):  
Stem Cells ◽  
Systems Biology ◽  
Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Temporal Dynamics ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Culture Conditions

Mouse embryonic stem cells (mESCs), derived from the inner cell mass of the blastocyst, are pluripotent stem cells having self-renewal capability and the potential of differentiating into every cell type under the appropriate culture conditions. An increasing number of reports have been published to uncover the molecular mechanisms that orchestrate pluripotency and cell fate specification using combined computational and experimental methodologies. Here, we review recent systems biology approaches to describe the causes and functions of gene expression heterogeneity and complex temporal dynamics of pluripotency markers in mESCs under uniform culture conditions. In particular, we focus on the dynamics of Nanog, a key regulator of the core pluripotency network and of mESC fate. We summarize the strengths and limitations of different experimental and modeling approaches and discuss how various strategies could be used.

Sign in / Sign up

Export Citation Format

Share Document