scholarly journals Diversity of fate outcomes in cell pairs under lateral inhibition

2015 ◽  
Author(s):  
Nara Guisoni ◽  
Rosa Martinez-Corral ◽  
Jordi Garcia Ojalvo ◽  
Joaquín de Navascués
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Lateral Inhibition ◽  
Contact Area ◽  
Activation Threshold ◽  
Cell Fate Decisions ◽  
The Standard Model ◽  
Summary Statement ◽  
Salt And Pepper ◽  
Isolated Cell

AbstractCell fate determination by lateral inhibition via Notch/Delta signalling has been extensively studied. Most formalised models consider Notch/Delta interactions in fields of cells, with parameters that typically lead to symmetry breaking of signalling states between neighbouring cells, commonly resulting in salt-and-pepper fate patterns. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of lateral inhibition can lead to stable symmetric signalling states. We apply this model to the adult intestinal stem cell (ISC) ofDrosophila, whose fate is stochastic but dependent on the Notch/Delta pathway. We observe a correlation between signalling state in cell pairs and their contact area. We interpret this behaviour in terms of the properties of our model in the presence of population variability in signalling thresholds. Our results suggest that the dynamics of Notch/Delta signalling can contribute to explain stochasticity in stem cell fate decisions, and that the standard model for lateral inhibition can account for a wider range of developmental outcomes than previously considered.Summary statementNotch/Delta-mediated lateral inhibition in cell pairs can result in symmetric signalling depending on the activation threshold, which can modulate cell-fate decisions depending on contact area.

scholarly journals Context-dependent roles of YAP/TAZ in stem cell fates and cancer

2021 ◽  
Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Cell ◽  
Substantial Portion ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cell Death Pathways ◽  
Multiple Context ◽  
Cancer Cell Survival ◽  
Context Dependent

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

scholarly journals Polyamine-controlled proliferation and protein biosynthesis are independent determinants of hair follicle stem cell fate

2020 ◽  
Author(s):  
Kira Allmeroth ◽  
Christine S. Kim ◽  
Andrea Annibal ◽  
Andromachi Pouikli ◽  
Carlos Andrés Chacón-Martínez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Cell Fate ◽  
Protein Biosynthesis ◽  
Mrna Translation ◽  
Stem Cell Differentiation ◽  
List Type ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Hair Follicle Stem Cell

AbstractStem cell differentiation is accompanied by an increase in mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine, and spermine that are essential for cell growth and stem cell maintenance. However, the role of polyamines as endogenous effectors of stem cell fate and whether they act through translational control remains obscure. Here, we investigated the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. HFSCs showed lower translation rates than progenitor cells, and a forced suppression of translation by direct targeting of the ribosome or through specific depletion of natural polyamines elevated stemness. In addition, we identified N1-acetylspermidine as a novel parallel regulator of cell fate decisions, increasing proliferation without reducing translation. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions.Key PointsLow mRNA translation rates characterize hair follicle stem cell (HFSC) stateDepletion of natural polyamines enriches HFSCs via reduced translationN1-acetylspermidine promotes HFSC state without reducing translationN1-acetylspermidine expands the stem cell pool through elevated proliferation

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control

2019 ◽  
Vol 97 (1) ◽  
pp. 10-20 ◽  
Author(s):  
Laura P.M.H. de Rooij ◽  
Derek C.H. Chan ◽  
Ava Keyvani Chahi ◽  
Kristin J. Hope
Keyword(s):  
Transcriptional Regulation ◽  
Stem Cell ◽  
Cell Fate ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Control Of Gene Expression ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Post Transcriptional Regulation

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA-binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation, or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSCs, its implications for normal, perturbed, and malignant hematopoiesis, and the most recent technological innovations aimed at RBP–RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Histone crotonylation regulates neural stem cell fate decisions by activating bivalent promoters

EMBO Reports ◽  
2021 ◽  
Author(s):  
Shang‐Kun Dai ◽  
Pei‐Pei Liu ◽  
Hong‐Zhen Du ◽  
Xiao Liu ◽  
Ya‐Jie Xu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Cell Fate Decisions

scholarly journals mRNA modification orchestrates cancer stem cell fate decisions

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Weicheng Liang ◽  
Zexiao Lin ◽  
Cong Du ◽  
Dongbo Qiu ◽  
Qi Zhang
Keyword(s):  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Cell Fate Decisions

scholarly journals Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions

PLoS Genetics ◽  
2011 ◽  
Vol 7 (6) ◽  
pp. e1002130 ◽  
Author(s):  
Kian Leong Lee ◽  
Sandy Keat Lim ◽  
Yuriy Lvovich Orlov ◽  
Le Yau Yit ◽  
Henry Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Activin Signaling
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