scholarly journals Cell fate transitions and the replication timing decision point

2010 ◽  
Vol 191 (5) ◽  
pp. 899-903 ◽  
Author(s):  
David M. Gilbert
Keyword(s):  
Cell Fate ◽  
Large Scale ◽  
Three Dimensional ◽  
Replication Timing ◽  
Window Of Opportunity ◽  
Decision Point ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Timing Decision ◽  
3D Architecture

Recent findings suggest that large-scale remodeling of three dimensional (3D) chromatin architecture occurs during a brief period in early G1 phase termed the replication timing decision point (TDP). In this speculative article, I suggest that the TDP may represent an as yet unappreciated window of opportunity for extracellular cues to influence 3D architecture during stem cell fate decisions. I also describe several testable predictions of this hypothesis.

scholarly journals Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2422
Author(s):  
Oleg Timofeev ◽  
Thorsten Stiewe
Keyword(s):  
Cancer Therapy ◽  
Dna Binding ◽  
Cell Fate ◽  
Tumor Suppression ◽  
Quaternary Structure ◽  
Three Dimensional ◽  
Structural Basis ◽  
Sequence Specificity ◽  
Cell Fate Decisions ◽  
Cancer Mutations

p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.

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

scholarly journals A mathematical model of mechanotransduction reveals how mechanical memory regulates mesenchymal stem cell fate decisions

2017 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Peng ◽  
Linan Liu ◽  
Adam L MacLean ◽  
Chi Wut Wong ◽  
Weian Zhao ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Fate ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Mechanical Memory

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 Control of cellular responses to mechanical cues through YAP/TAZ regulation

2019 ◽  
Vol 294 (46) ◽  
pp. 17693-17706 ◽  
Author(s):  
Ishani Dasgupta ◽  
Dannel McCollum
Keyword(s):  
Cell Fate ◽  
Wound Repair ◽  
Hippo Pathway ◽  
Three Dimensional ◽  
Focal Adhesions ◽  
Mechanical Stimuli ◽  
Cell Contractility ◽  
Cell Fate Decisions ◽  
Disease States ◽  
The Hippo Pathway

To perceive their three-dimensional environment, cells and tissues must be able to sense and interpret various physical forces like shear, tensile, and compression stress. These forces can be generated both internally and externally in response to physical properties, like substrate stiffness, cell contractility, and forces generated by adjacent cells. Mechanical cues have important roles in cell fate decisions regarding proliferation, survival, and differentiation as well as the processes of tissue regeneration and wound repair. Aberrant remodeling of the extracellular space and/or defects in properly responding to mechanical cues likely contributes to various disease states, such as fibrosis, muscle diseases, and cancer. Mechanotransduction involves the sensing and translation of mechanical forces into biochemical signals, like activation of specific genes and signaling cascades that enable cells to adapt to their physical environment. The signaling pathways involved in mechanical signaling are highly complex, but numerous studies have highlighted a central role for the Hippo pathway and other signaling networks in regulating the YAP and TAZ (YAP/TAZ) proteins to mediate the effects of mechanical stimuli on cellular behavior. How mechanical cues control YAP/TAZ has been poorly understood. However, rapid progress in the last few years is beginning to reveal a surprisingly diverse set of pathways for controlling YAP/TAZ. In this review, we will focus on how mechanical perturbations are sensed through changes in the actin cytoskeleton and mechanosensors at focal adhesions, adherens junctions, and the nuclear envelope to regulate YAP/TAZ.

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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