scholarly journals Cell Fate Control by Translation: mRNA Translation Initiation as a Therapeutic Target for Cancer Development and Stem Cell Fate Control

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 665 ◽  
Author(s):  
Hyun-Jung Kim
Keyword(s):  
Protein Synthesis ◽  
Stem Cell ◽  
Cell Fate ◽  
Translation Initiation ◽  
Mrna Translation ◽  
Cancer Development ◽  
Cell Behavior ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Cell Fate Control

Translation of mRNA is an important process that controls cell behavior and gene regulation because proteins are the functional molecules that determine cell types and function. Cancer develops as a result of genetic mutations, which lead to the production of abnormal proteins and the dysregulation of translation, which in turn, leads to aberrant protein synthesis. In addition, the machinery that is involved in protein synthesis plays critical roles in stem cell fate determination. In the current review, recent advances in the understanding of translational control, especially translational initiation in cancer development and stem cell fate control, are described. Therapeutic targets of mRNA translation such as eIF4E, 4EBP, and eIF2, for cancer treatment or stem cell fate regulation are reviewed. Upstream signaling pathways that regulate and affect translation initiation were introduced. It is important to regulate the expression of protein for normal cell behavior and development. mRNA translation initiation is a key step to regulate protein synthesis, therefore, identifying and targeting molecules that are critical for protein synthesis is necessary and beneficial to develop cancer therapeutics and stem cells fate regulation.

Neural Stem Cell Fate Control on Micropatterned Substrates

2017 ◽  
pp. 19-44 ◽  
Author(s):  
Leonora Buzanska ◽  
Marzena Zychowicz ◽  
Ana Ruiz ◽  
François Rossi
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Cell Fate Control

scholarly journals ANALYSIS OF INTRACELLULAR SIGNALING KINETICS PREDICTS PRESENTATION MODES AND TARGETS FOR STEM CELL FATE CONTROL

2005 ◽  
Vol preprint (2007) ◽  
pp. e130
Author(s):  
Alborz Mahdavi ◽  
Ryan E Davey ◽  
Patrick Bhola ◽  
Ting Yin ◽  
Peter W Zandstra
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Intracellular Signaling ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Presentation Modes ◽  
Cell Fate Control

scholarly journals Nanotopographical surfaces for stem cell fate control: Engineering mechanobiology from the bottom

Nano Today ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. 759-784 ◽  
Author(s):  
Weiqiang Chen ◽  
Yue Shao ◽  
Xiang Li ◽  
Gang Zhao ◽  
Jianping Fu
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Engineering ◽  
Stem Cell Fate ◽  
Fate Control ◽  
Cell Fate Control

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 Hydrogels Containing Gradients in Vascular Density Reveal Dose-Dependent Role of Angiocrine Cues on Stem Cell Behavior

2021 ◽  
Author(s):  
Mai T. Ngo ◽  
Victoria R. Barnhouse ◽  
Aidan E. Gilchrist ◽  
Christine J. Hunter ◽  
Joy N. Hensold ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Cell Behavior ◽  
Vascular Density ◽  
Microfluidic Mixing ◽  
Hematopoietic Stem ◽  
Stem Cell Fate ◽  
Signaling Axis ◽  
Dose Dependent

AbstractBiomaterials that replicate patterns of microenvironmental signals from the stem cell niche offer the potential to refine platforms to regulate stem cell behavior. While significant emphasis has been placed on understanding the effects of biophysical and biochemical cues on stem cell fate, vascular-derived or angiocrine cues offer an important alternative signaling axis for biomaterial-based stem cell platforms. Elucidating dose-dependent relationships between angiocrine cues and stem cell fate are largely intractable in animal models and two-dimensional cell culture. In this study, we leverage microfluidic mixing devices to generate three-dimensional hydrogels containing lateral gradients in vascular density alongside murine hematopoietic stem cells (HSCs). Regional differences in vascular density can be generated via embossed gradients in cell, matrix, or growth factor density. HSCs co-cultured alongside vascular gradients reveal spatial patterns of HSC phenotype in response to angiocrine signals. Notably, decreased Akt signaling in high vessel density regions led to increased expansion of lineage-positive hematopoietic cells. This approach offers a combinatorial tool to rapidly screen a continuum of microenvironments with varying vascular, biophysical, and biochemical cues to reveal the influence of local angiocrine signals on HSC fate.

scholarly journals Drosophila as a Model for Developmental Biology: Stem Cell-Fate Decisions in the Developing Nervous System

2018 ◽  
Vol 6 (4) ◽  
pp. 25 ◽  
Author(s):  
Katherine Harding ◽  
Kristin White
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Behavior ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Unique System ◽  
Developing Nervous System

Stem cells face a diversity of choices throughout their lives. At specific times, they may decide to initiate cell division, terminal differentiation, or apoptosis, or they may enter a quiescent non-proliferative state. Neural stem cells in the Drosophila central nervous system do all of these, at stereotypical times and anatomical positions during development. Distinct populations of neural stem cells offer a unique system to investigate the regulation of a particular stem cell behavior, while comparisons between populations can lead us to a broader understanding of stem cell identity. Drosophila is a well-described and genetically tractable model for studying fundamental stem cell behavior and the mechanisms that underlie cell-fate decisions. This review will focus on recent advances in our understanding of the factors that contribute to distinct stem cell-fate decisions within the context of the Drosophila nervous system.

scholarly journals N1-acetylspermidine is a determinant of hair follicle stem cell fate

2021 ◽  
Vol 134 (9) ◽  
Author(s):  
Kira Allmeroth ◽  
Christine S. Kim ◽  
Andrea Annibal ◽  
Andromachi Pouikli ◽  
Janis Koester ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Cell Fate ◽  
Translational Control ◽  
Mrna Translation ◽  
Stem Cell Differentiation ◽  
Stem Cell Fate ◽  
Cell Fate Decisions ◽  
Hair Follicle Stem Cell

ABSTRACT Stem cell differentiation is accompanied by increased mRNA translation. The rate of protein biosynthesis is influenced by the polyamines putrescine, spermidine and spermine, which 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 investigate the function of polyamines in stem cell fate decisions using hair follicle stem cell (HFSC) organoids. Compared to progenitor cells, HFSCs showed lower translation rates, correlating with reduced polyamine levels. Surprisingly, overall polyamine depletion decreased translation but did not affect cell fate. In contrast, specific depletion of natural polyamines mediated by spermidine/spermine N1-acetyltransferase (SSAT; also known as SAT1) activation did not reduce translation but enhanced stemness. These results suggest a translation-independent role of polyamines in cell fate regulation. Indeed, we identified N1-acetylspermidine as a determinant of cell fate that acted through increasing self-renewal, and observed elevated N1-acetylspermidine levels upon depilation-mediated HFSC proliferation and differentiation in vivo. Overall, this study delineates the diverse routes of polyamine metabolism-mediated regulation of stem cell fate decisions. This article has an associated First Person interview with the first author of the paper.

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