scholarly journals Systems biology provides new insights into the molecular mechanisms that control the fate of embryonic stem cells

2011 ◽  
Vol 227 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Sunil K. Mallanna ◽  
Angie Rizzino
Keyword(s):  
Stem Cells ◽  
Systems Biology ◽  
Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem

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.

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.

Systems Biology Approach Identifies the Kinase Csnk1a1 as a Regulator of the DNA Damage Response in Embryonic Stem Cells

2013 ◽  
Vol 6 (259) ◽  
pp. ra5-ra5 ◽  
Author(s):  
J. Carreras Puigvert ◽  
L. von Stechow ◽  
R. Siddappa ◽  
A. Pines ◽  
M. Bahjat ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Systems Biology ◽  
Embryonic Stem Cells ◽  
Dna Damage Response ◽  
Embryonic Stem ◽  
Damage Response

scholarly journals Definitive-like erythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1515-1523 ◽  
Author(s):  
Kai-Hsin Chang ◽  
Angelique M. Nelson ◽  
Hua Cao ◽  
Linlin Wang ◽  
Betty Nakamoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Embryoid Body ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Erythroid Differentiation ◽  
Erythroid Cells ◽  
Promising Tool

Human embryonic stem cells are a promising tool to study events associated with the earliest ontogenetic stages of hematopoiesis. We describe the generation of erythroid cells from hES (H1) by subsequent processing of cells present at early and late stages of embryoid body (EB) differentiation. Kinetics of hematopoietic marker emergence suggest that CD45+ hematopoiesis peaks at late D14EB differentiation stages, although low-level CD45- erythroid differentiation can be seen before that stage. By morphologic criteria, hES-derived erythroid cells were of definitive type, but these cells both at mRNA and protein levels coexpressed high levels of embryonic (ϵ) and fetal (γ) globins, with little or no adult globin (β). This globin expression pattern was not altered by the presence or absence of fetal bovine serum, vascular endothelial growth factor, Flt3-L, or coculture with OP-9 during erythroid differentiation and was not culture time dependent. The coexpression of both embryonic and fetal globins by definitive-type erythroid cells does not faithfully mimic either yolk sac embryonic or their fetal liver counterparts. Nevertheless, the high frequency of erythroid cells coexpressing embryonic and fetal globin generated from embryonic stem cells can serve as an invaluable tool to further explore molecular mechanisms.

scholarly journals RNA-Seq analysis reveals pluripotency-associated genes and their interaction networks in human embryonic stem cells

2019 ◽  
Author(s):  
Arindam Ghosh ◽  
Anup Som
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Molecular Mechanisms ◽  
Gene List ◽  
Experimental Studies ◽  
Embryonic Stem ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Differentiation Markers

Insight into the key genes of pluripotency in human and their interrelationships is necessary for understanding the underlying mechanism of pluripotency and hence their successful application in regenerative medicine. The recent advances in transcriptomics technologies have created new opportunities to decipher the genes involved in pluripotency, genetic network that governs the unique properties of embryonic stem cells and lineage differentiation mechanisms in a deeper scale. There are a large number of experimental studies on human embryonic stem cells (hESCs) being routinely conducted for unfolding the underlying biology of embryogenesis and their clinical prospects. However, the outcome of these studies often lacks consensus due to differences in samples, experimental techniques and/or analysis protocols. A universal stemness gene list is still lacking. In this quest, we compared transcriptomic profiles of pluripotent and non-pluripotent samples from diverse cell lines/types generated through RNA-sequencing (RNA-seq). We used a uniform pipeline for the analysis of raw RNA-seq data in order to reduce the amount of variation. Our analysis revealed a consensus set of 498 pluripotency-associated genes and 432 genes as potential pluripotent cell differentiation markers. Furthermore, we predicted 32 genes as "pluripotency critical genes". Reconstruction and analysis of co-expression networks further highlighted the importance of these genes. Gene ontology (GO) and pathway enrichment analysis, StemChecker and literature survey confirmed the involvement of the genes in the induction and maintenance of pluripotency, though more experimental studies are required for understanding their molecular mechanisms in human.

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 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.

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