scholarly journals A Novel Taxon of RNA Viruses Endemic to Planarian Flatworms

2019 ◽  
Author(s):  
Jeffrey Burrows ◽  
Delphine Depierreux ◽  
Max L. Nibert ◽  
Bret J. Pearson
Keyword(s):  
Stem Cell ◽  
Rna Interference ◽  
Persistent Infection ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Adult Stem Cell ◽  
Dsrna Virus ◽  
Rnai Pathway ◽  
Cell Type

AbstractThe phylum Platyhelminthes is composed of both parasitic and non-parasitic flatworms. While the parasitic species have drawn attention for their wide effects on human and livestock heath, free-living flatworms, such as freshwater planarians, have become molecular models of regeneration and stem cell biology in the laboratory. However, one aspect of planarian biology that remains understudied is the relationship between host and any endemic viruses. Here we used searches of multiple transcriptomes from Schmidtea mediterranea asexual strain CIW4 and detected a novel, double-stranded RNA (dsRNA) virus, named S. mediterranea tricladivirus (SmedTV), which represents a distinct taxon (proposed new genus) within a larger taxon of monosegmented dsRNA viruses of diverse hosts. Experimental evidence for SmedTV in S. mediterranea CIW4 was obtained through whole-mount in situ hybridization (WISH). SmedTV “expression” (detected by both sense and anti-sense probes) was discrete yet variable from worm to worm and cell type to cell type, suggesting a persistent infection. Single-cell RNA sequencing (scRNAseq) further supported that SmedTV expression was low in stem cells, but substantially higher in multiple, though not all, differentiated tissues, with notable neural enrichment.Interestingly, knockdown of SmedTV by RNA-interference resulted in a “cure” of SmedTV after 10 RNAi doses, and expression remained undetectable by WISH even after 90 days. Due to being able to evade host defenses and the endogenous RNAi pathway, we believe SmedTV represents a novel animal model to study host-virus evolution.Statement of significancePlanarians are freshwater flatworms and emerging models to study the molecular mechanisms of adult stem cell and regenerative biology. However, they also live in aquatic environments with high amounts of viruses, bacteria, fungi, and protist pathogens. How the planarian immune system copes with all of these is largely unknown and only 2 types of virus have been described. Here we find a novel dsRNA virus, endemic to multiple types of flatworms. We show that it is a persistent infection, and likely transmits from stem cell to differentiated cell in the planarian, while avoiding endogenous RNA-interference machinery and mechanisms used to suppress viruses. We present this as a new model to study host-virus defense and evolution.

scholarly journals Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cell ◽  
Physical Exercise ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Heart Function ◽  
Stem Cell Biology ◽  
Myocardial Repair ◽  
Beneficial Effects

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

scholarly journals Cell-type specific in vitro gene expression profiling of stem-cell derived neural models

2020 ◽  
Author(s):  
James A. Gregory ◽  
Emily Hoelzli ◽  
Rawan Abdelaal ◽  
Catherine Braine ◽  
Miguel Cuevas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Induced Pluripotent Stem Cell ◽  
Underlying Disease ◽  
Mouse Tissue ◽  
Cell Type ◽  
Primary Mouse ◽  
Cell Type Specific

AbstractGenetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease, but also challenge our ability to resolve cell-type specific perturbations. Here we report an extension of the RiboTag system, first developed to achieve cell-type restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables efficient depletion of off-target RNA in mixed species primary co-cultures and in hiPSC-derived neural progenitor cells, motor neurons, and GABAergic neurons. Nonetheless, depletion efficiency varies across independent experimental replicates. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.

scholarly journals Insights into neural stem cell biology from flies

2007 ◽  
Vol 363 (1489) ◽  
pp. 39-56 ◽  
Author(s):  
Boris Egger ◽  
James M Chell ◽  
Andrea H Brand
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Neurological Injury ◽  
Temporal Regulation ◽  
Stem Cell Maintenance ◽  
Different Types ◽  
Made In

Drosophila neuroblasts are similar to mammalian neural stem cells in their ability to self-renew and to produce many different types of neurons and glial cells. In the past two decades, great advances have been made in understanding the molecular mechanisms underlying embryonic neuroblast formation, the establishment of cell polarity and the temporal regulation of cell fate. It is now a challenge to connect, at the molecular level, the different cell biological events underlying the transition from neural stem cell maintenance to differentiation. Progress has also been made in understanding the later stages of development, when neuroblasts become mitotically inactive, or quiescent, and are then reactivated postembryonically to generate the neurons that make up the adult nervous system. The ability to manipulate the steps leading from quiescence to proliferation and from proliferation to differentiation will have a major impact on the treatment of neurological injury and neurodegenerative disease.

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.

Signaling pathways governing stem-cell fate

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 492-503 ◽  
Author(s):  
Ulrika Blank ◽  
Göran Karlsson ◽  
Stefan Karlsson
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Cell Fate ◽  
Cell Biology ◽  
Adult Stem Cell ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Recent Developments ◽  
Molecular Machinery

Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem-cell biology for several decades. However, paradoxically, although HSCs can be defined by function and even purified to near-homogeneity, the intricate molecular machinery and the signaling mechanisms regulating fate events, such as self-renewal and differentiation, have remained elusive. Recently, several developmentally conserved signaling pathways have emerged as important control devices of HSC fate, including Notch, Wingless-type (Wnt), Sonic hedgehog (Shh), and Smad pathways. HSCs reside in a complex environment in the bone marrow, providing a niche that optimally balances signals that control self-renewal and differentiation. These signaling circuits provide a valuable structure for our understanding of how HSC regulation occurs, concomitantly with providing information of how the bone marrow microenvironment couples and integrates extrinsic with intrinsic HSC fate determinants. It is the focus of this review to highlight some of the most recent developments concerning signaling pathways governing HSC fate.

scholarly journals Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro

2021 ◽  
Vol 22 (4) ◽  
pp. 1998
Author(s):  
Anna Laura Voigt ◽  
Shiama Thiageswaran ◽  
Nathalia de Lima e Martins Lara ◽  
Ina Dobrinski
Keyword(s):  
Stem Cell ◽  
Cell Biology ◽  
Current Knowledge ◽  
Adult Stem Cell ◽  
Spermatogonial Stem Cell ◽  
Testicular Development ◽  
Cell Integrity ◽  
In Vitro Expansion

The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding the factors that are necessary for lifelong maintenance of a SSC pool in vivo is essential for successful in vitro expansion and safe downstream clinical usage. This review focused on the current knowledge of prepubertal testicular development and germ cell metabolism in different species, and implications for translational medicine. The significance of metabolism for cell biology, stem cell integrity, and fate decisions is discussed in general and in the context of SSC in vivo maintenance, differentiation, and in vitro expansion.

scholarly journals Novel Pituitary Organoid Model as Powerful Tool to Unravel Pituitary Stem Cell Biology Across Ages and Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A652-A652
Author(s):  
Hugo E J Vankelecom ◽  
Emma Laporte ◽  
Florian Hermans ◽  
Charlotte Nys ◽  
Annelies Vennekens
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Cell Activation ◽  
Stem Cell Biology ◽  
Cell Compartment ◽  
Organoid Culture ◽  
Stem Cell Compartment

Abstract The pituitary gland harbors a population of stem cells. However, role and regulation of these cells remain poorly understood. We recently established organoids from mouse pituitary as a novel research tool to explore pituitary stem cell biology (Cox et al., J. Endocrinol. 2019; 240:287-308). In general, organoids represent 3D in vitro cell configurations that develop and self-organize from (single) tissue stem cells under well-defined culture conditions that typically mirror the stem cell niche and/or embryogenic processes. Organoids reliably recapitulate key aspects of the original organ, including of its stem cell compartment. Moreover, organoids are long-term expandable while retaining these properties. We demonstrated that pituitary organoids originate from the resident (SOX2+) stem cells, largely phenocopy these cells and retain the stemness phenotype during expansive culture. Interestingly, the organoids show confident in vivo translatability and, when developed from transgenically damaged gland, recapitulate the activation status of the stem cells as observed in situ following injury. Now, we found that the organoids also mirror the stem cells’ phenotype and biology in physiological conditions in which the stem cell compartment is either activated or compromised. Organoids from the neonatal maturing pituitary reproduce phenotypical and functional aspects of its activated stem cells, whereas organoids from aging gland mimic the declined functional state of the stem cells in old pituitary. Interestingly, this functional decay was found to be reverted during organoid culture, indicating that the old pituitary stem cells retain intrinsic functionality but are in vivo restrained by an obstructive microenvironment, not present in the organoid culture. Indeed, using single-cell transcriptomics and in vivo analysis, we found that the aging pituitary suffers from a prevailing inflammatory state (inflammaging) which appears to raise the threshold for stem cell activation. Interestingly, comparison of young and old pituitary led us to the discovery of pituitary stem cell activators. Finally, we found that activated parameters of organoid formation are also observed when tumorigenesis takes place in the gland, again mimicking the in situ stem cell activation that is occurring in this perturbed, pathological condition. Taken together, we identified, and applied, our new pituitary organoid model as advanced and powerful tool to gain profound insight into pituitary stem cell behavior across life and disease, which is expected to eventually translate into restorative and rejuvenative tactics when pituitary function is compromised by damage or age. In this context, our single-cell transcriptome database has strong potential to unveil appealing targets.

scholarly journals Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1406
Author(s):  
James A. Gregory ◽  
Emily Hoelzli ◽  
Rawan Abdelaal ◽  
Catherine Braine ◽  
Miguel Cuevas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Induced Pluripotent Stem Cell ◽  
Underlying Disease ◽  
Mouse Tissue ◽  
Cell Type ◽  
Primary Mouse ◽  
Cell Type Specific

Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.

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