scholarly journals Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release

2013 ◽  
Vol 201 (5) ◽  
pp. 741-757 ◽  
Author(s):  
Tiffiney R. Hartman ◽  
Todd I. Strochlic ◽  
Yingbiao Ji ◽  
Daniel Zinshteyn ◽  
Alana M. O’Reilly
Keyword(s):  
Stem Cell ◽  
Egg Production ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Transmembrane Protein ◽  
Dietary Cholesterol ◽  
Adult Stem Cell ◽  
Specific Response ◽  
Molecular Control ◽  
Stem Cell Divisions

A healthy diet improves adult stem cell function and delays diseases such as cancer, heart disease, and neurodegeneration. Defining molecular mechanisms by which nutrients dictate stem cell behavior is a key step toward understanding the role of diet in tissue homeostasis. In this paper, we elucidate the mechanism by which dietary cholesterol controls epithelial follicle stem cell (FSC) proliferation in the fly ovary. In nutrient-restricted flies, the transmembrane protein Boi sequesters Hedgehog (Hh) ligand at the surface of Hh-producing cells within the ovary, limiting FSC proliferation. Upon feeding, dietary cholesterol stimulates S6 kinase–mediated phosphorylation of the Boi cytoplasmic domain, triggering Hh release and FSC proliferation. This mechanism enables a rapid, tissue-specific response to nutritional changes, tailoring stem cell divisions and egg production to environmental conditions sufficient for progeny survival. If conserved in other systems, this mechanism will likely have important implications for studies on molecular control of stem cell function, in which the benefits of low calorie and low cholesterol diets are beginning to emerge.

Epigenetic control of adult stem cell function

2016 ◽  
Vol 17 (10) ◽  
pp. 643-658 ◽  
Author(s):  
Alexandra Avgustinova ◽  
Salvador Aznar Benitah
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Adult Stem Cell ◽  
Epigenetic Control

scholarly journals Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Christian Kosan ◽  
Maren Godmann
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Quiescent State ◽  
Ongoing Research ◽  
Hematopoietic Stem ◽  
Lineage Differentiation ◽  
Multipotent Progenitor Cells

All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

scholarly journals Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism in Drosophila

2018 ◽  
Author(s):  
Rebecca Obniski ◽  
Matthew Sieber ◽  
Allan C. Spradling
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Notch Signaling ◽  
Cell Function ◽  
Dietary Cholesterol ◽  
Adult Life ◽  
Notch Pathway ◽  
Stem Cell Differentiation ◽  
Nuclear Hormone Receptor ◽  
Dietary Lipids

SummaryTissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with developmental pathways. Using the Drosophila midgut as a model we found that during the first four days of adult life, dietary lipids including cholesterol, determine how many enteroendocrine (ee) cells differentiate and persist in the posterior midgut where lipids are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, and utilization, is required for sterol-mediated changes in ee number. Dietary cholesterol influences new intestinal epithelial cell differentiation from stem cells by altering the level and persistance of Notch signaling. Exogenous lipids modulate signaling by changing the stability of the Delta ligand and Notch intracellular domain and their trafficking in endosomal vesicles. Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues such as the ovary, suggesting that Delta trafficking in many cells is sensitive to cellular sterol levels. These diet-mediated alterations in ee number in young animals contribute to a metabolic program adapted to the prevailing nutrient environment that persists after the diet changes. A low sterol diet also slows the proliferation of enteroendocrine tumors initiated by disruptions in the Notch pathway. These studies show that a specific dietary nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation and cause lasting changes in tissue structure and physiology.

scholarly journals Molecular mechanisms mediating asymmetric subcellular localisation of the core planar polarity pathway proteins

2020 ◽  
Vol 48 (4) ◽  
pp. 1297-1308 ◽  
Author(s):  
Carl Harrison ◽  
Hongyu Shao ◽  
Helen Strutt ◽  
David Strutt
Keyword(s):  
Molecular Interactions ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Subcellular Localisation ◽  
Cellular Polarity ◽  
Planar Polarity ◽  
Molecular Control ◽  
Post Translational Modifications ◽  
The Core ◽  
Core Proteins

Planar polarity refers to cellular polarity in an orthogonal plane to apicobasal polarity, and is seen across scales from molecular distributions of proteins to tissue patterning. In many contexts it is regulated by the evolutionarily conserved ‘core' planar polarity pathway that is essential for normal organismal development. Core planar polarity pathway components form asymmetric intercellular complexes that communicate polarity between neighbouring cells and direct polarised cell behaviours and the formation of polarised structures. The core planar polarity pathway consists of six structurally different proteins. In the fruitfly Drosophila melanogaster, where the pathway is best characterised, an intercellular homodimer of the seven-pass transmembrane protein Flamingo interacts on one side of the cell junction with the seven-pass transmembrane protein Frizzled, and on the other side with the four-pass transmembrane protein Strabismus. The cytoplasmic proteins Diego and Dishevelled are co-localised with Frizzled, and Prickle co-localises with Strabismus. Between these six components there are myriad possible molecular interactions, which could stabilise or destabilise the intercellular complexes and lead to their sorting into polarised distributions within cells. Post-translational modifications are key regulators of molecular interactions between proteins. Several post-translational modifications of core proteins have been reported to be of functional significance, in particular phosphorylation and ubiquitination. In this review, we discuss the molecular control of planar polarity and the molecular ecology of the core planar polarity intercellular complexes. Furthermore, we highlight the importance of understanding the spatial control of post-translational modifications in the establishment of planar polarity.

scholarly journals The Role of MicroRNAs in Cardiac Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Nima Purvis ◽  
Andrew Bahn ◽  
Rajesh Katare
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Cardiac Stem Cells ◽  
Cell Therapies ◽  
Small Noncoding Rna ◽  
Proliferation And Differentiation

Stem cells are considered as the next generation drug treatment in patients with cardiovascular disease who are resistant to conventional treatment. Among several stem cells used in the clinical setting, cardiac stem cells (CSCs) which reside in the myocardium and epicardium of the heart have been shown to be an effective option for the source of stem cells. In normal circumstances, CSCs primarily function as a cell store to replace the physiologically depleted cardiovascular cells, while under the diseased condition they have been shown to experimentally regenerate the diseased myocardium. In spite of their major functional role, molecular mechanisms regulating the CSCs proliferation and differentiation are still unknown. MicroRNAs (miRs) are small, noncoding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have demonstrated the important role of miRs in regulating stem cell proliferation and differentiation, as well as other physiological and pathological processes related to stem cell function. This review summarises the current understanding of the role of miRs in CSCs. A deeper understanding of the mechanisms by which miRs regulate CSCs may lead to advances in the mode of stem cell therapies for the treatment of cardiovascular diseases.

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