scholarly journals Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models

2019 ◽  
Vol 20 (2) ◽  
pp. 455 ◽  
Author(s):  
Felix Beyer ◽  
Iria Samper Agrelo ◽  
Patrick Küry
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Ex Vivo ◽  
Meta Analysis ◽  
Cell Types ◽  
Adult Brain ◽  
Repair Capacity ◽  
Cell Fate Decisions ◽  
Limiting Parameters

The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter.

Abstract 3451: Interactions between N-myc and Sox9 promote medulloblastoma and determine cell fate decisions in cerebellar neural stem cells

2011 ◽  
Author(s):  
Fredrik J. Swartling ◽  
Anders I. Persson ◽  
Jasmine Lau ◽  
Paul A. Northcott ◽  
Matthew R. Grimmer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Cell Fate Decisions

scholarly journals Mitochondrial Control of Stem Cell State and Fate: Lessons From Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Satish Kumar Tiwari ◽  
Sudip Mandal
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Types ◽  
Extrinsic Factors ◽  
Cell Fate Decisions ◽  
Cell State ◽  
Resident Stem Cells ◽  
Stem Cell State

Over the years, Drosophila has served as a wonderful genetically tractable model system to unravel various facets of tissue-resident stem cells in their microenvironment. Studies in different stem and progenitor cell types of Drosophila have led to the discovery of cell-intrinsic and extrinsic factors crucial for stem cell state and fate. Though initially touted as the ATP generating machines for carrying various cellular processes, it is now increasingly becoming clear that mitochondrial processes alone can override the cellular program of stem cells. The last few years have witnessed a surge in our understanding of mitochondria’s contribution to governing different stem cell properties in their subtissular niches in Drosophila. Through this review, we intend to sum up and highlight the outcome of these in vivo studies that implicate mitochondria as a central regulator of stem cell fate decisions; to find the commonalities and uniqueness associated with these regulatory mechanisms.

DNA Methylation Abnormality and Brain Dysfunction of Neural Stem Cells Caused by Chronic Inflammation by Nanoparticle Exposure

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 28-30
Author(s):  
Ken Tachibana
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neural Development ◽  
Broad Class ◽  
Cell Types ◽  
Associate Professor ◽  
Adult Brain ◽  
Wide Range ◽  
The Creation ◽  
The Brain

The biological development of a human is an extremely complex and delicate process. It starts from fertilisation and continues until long after birth. The creation and development of the brain is particularly complicated and susceptible to disruptions to its progression. The primary cells responsible for the development of the brain are the neural stem cells. These are a broad class of cells that can differentiate into the wide range of cell types that form the adult brain. To achieve this complex process, different cells need to undergo a range of gene expression changes at the right time. This is delicate and its disturbance is a key cause of pathology in a wide range of diseases. There are many external factors that are known to disrupt neural development however, there are several common chemicals whose effects remain largely unknown. One such group are broadly described as nanoparticles. These are small particles that are being increasingly used by many industries as they can help in the creation of products with better properties. However, their effect on the environment and the human body – particularly that of a developing brain – have been largely unexamined. Associate Professor Ken Tachibana of the Division of Hygienic Chemistry, Sanyo-Onoda City University, Japan is researching the effects of nanoparticles on neural development.

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 Interactions between axon-like projections extended by Drosophila Follicle Stem Cells dictate cell fate decisions

2020 ◽  
Author(s):  
Eric H. Lee ◽  
Daniel Zinshteyn ◽  
Melissa Wang ◽  
Jessica Reinach ◽  
Cindy Chau ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Axon Growth ◽  
Cell Types ◽  
Still Life ◽  
Self Renewal ◽  
Cell Fate Decisions ◽  
Fate Decision ◽  
Tissue Aging ◽  
Follicle Stem Cells

AbstractStem cells cycle between periods of quiescence and proliferation to promote healthy tissue aging. Once proliferation is initiated, mechanisms that control the balance between self-renewal and differentiation must be engaged to ensure maintenance of stem cell pools until the next quiescent cycle occurs. Here, we demonstrate that dynamic axon-like projections extended by Follicle Stem Cells (FSCs) in the Drosophila ovary control the self-renewal-differentiation balance. Known axon growth regulators still life and sickie are necessary and sufficient for FSC projection growth, mediating organization of germline cyst architecture during follicle formation, controlling targeting of projections to FSCs or germ cells, and regulating expression of the cell fate determinants Eyes Absent (Eya) and Castor (Cas). Our results support a model in which FSC projections function similarly to axons, providing structural organization to a dynamic organ while mediating communication between distinct cell types to effect the key cell fate decision to self-renew or differentiate.

scholarly journals Safb1 regulates cell fate determination in adult neural stem cells by enhancing Drosha cleavage of NFIB mRNA

2021 ◽  
Author(s):  
Nikolas Ifflander ◽  
Chiara Rolando ◽  
Elli-Anna Balta ◽  
Pascal Forcella ◽  
Tanzila Mukhtar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Adult Brain ◽  
Specific Gene ◽  
Transcriptional Level ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Attachment Factor ◽  
Brain Homeostasis

During brain homeostasis, stem cell fate determination is crucial to guarantee function, adaptation and regeneration while preventing neurodegeneration and cognitive impairment. How neural stem cells (NSCs) are instructed to generate neurons or glia is not well understood. Here we addressed how fate is resolved in multipotent adult hippocampal NSCs, and identify Scaffold Attachment Factor B1 (Safb1) as a determinant of neuron production by blocking glial commitment. Safb1 is sufficient to block oligodendrocytic differentiation of NSCs by preventing expression of the transcription factor NFIB at the post-transcriptional level. Detailed interrogation of the Drosha interactome and functional validation revealed that Safb1 enhances NFIB mRNA cleavage in a Drosha-dependent fashion. Thus, our study provides a cellular mechanism for selective NSC fate regulation by post-transcriptional destabilization of mRNAs. Given the importance of NSC maintenance and fate determination in the adult brain, our findings have major implications for cell-specific gene expression, brain disease and aging.

scholarly journals Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

2017 ◽  
Author(s):  
Maria Angeles Marques-Torrejon ◽  
Ester Gangoso ◽  
Steven M. Pollard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Ex Vivo ◽  
Brain Slices ◽  
Genetically Engineered ◽  
Adult Brain ◽  
Host Interactions ◽  
The Brain

AbstractGlioblastoma (GBM) is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as GBM stem cells (GSCs). Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM tumours can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human). Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring of live cell behaviours. Here we explored whole adult brain coronal organotypic slices as a complementary strategy to remove the experimental bottleneck. Mouse adult brain slices remain viable in a neural stem cell serum-free basal media for several weeks. GSCs can therefore be easily microinjected into specific anatomical sites ex vivo. We demonstrated distinct responses of engrafted GSCs to different microenvironments in the brain. Within the subependymal zone – one of the adult neural stem cell niches – a subset of injected tumour cells could effectively engraft and respond to endothelial niche signals. GSCs transplanted slices were treated with the anti-mitotic drug temozolomide as proof-of-principle of the utility in modelling responses to existing treatments. Thus, engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices provides a convenient experimental model for studies of GSC-host interactions and preclinical testing of candidate therapeutic agents.

scholarly journals Research and therapy with induced pluripotent stem cells (iPSCs): social, legal, and ethical considerations

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sharif Moradi ◽  
Hamid Mahdizadeh ◽  
Tomo Šarić ◽  
Johnny Kim ◽  
Javad Harati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Cell Types ◽  
Healthy Person ◽  
New Drugs ◽  
Full Potential ◽  
Cell Fate Decisions ◽  
Induced Pluripotent

AbstractInduced pluripotent stem cells (iPSCs) can self-renew indefinitely in culture and differentiate into all specialized cell types including gametes. iPSCs do not exist naturally and are instead generated (“induced” or “reprogrammed”) in culture from somatic cells through ectopic co-expression of defined pluripotency factors. Since they can be generated from any healthy person or patient, iPSCs are considered as a valuable resource for regenerative medicine to replace diseased or damaged tissues. In addition, reprogramming technology has provided a powerful tool to study mechanisms of cell fate decisions and to model human diseases, thereby substantially potentiating the possibility to (i) discover new drugs in screening formats and (ii) treat life-threatening diseases through cell therapy-based strategies. However, various legal and ethical barriers arise when aiming to exploit the full potential of iPSCs to minimize abuse or unauthorized utilization. In this review, we discuss bioethical, legal, and societal concerns associated with research and therapy using iPSCs. Furthermore, we present key questions and suggestions for stem cell scientists, legal authorities, and social activists investigating and working in this field.

scholarly journals Cell-cell communication through FGF4 generates and maintains robust proportions of differentiated cell fates in embryonic stem cells

2020 ◽  
Author(s):  
Dhruv Raina ◽  
Angel Stanoev ◽  
Azra Bahadori ◽  
Michelle Protzek ◽  
Aneta Koseska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Fate ◽  
Initial Conditions ◽  
Embryonic Stem ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Cell Cell

AbstractDuring embryonic development and tissue homeostasis, reproducible proportions of differentiated cell types need to be specified from homogeneous precursor cell populations. How this is achieved despite uncertainty in initial conditions in the precursor cells, and how proportions are re-established upon perturbations in the developing tissue is not known. Here we report the differentiation of robust proportions of epiblast- and primitive endoderm-like cells from a wide range of experimentally controlled initial conditions in mouse embryonic stem cells. We demonstrate both experimentally and theoretically that recursive cell-cell communication via FGF4 establishes a population-based mechanism that generates and maintains robust proportions of differentiated cell types. Furthermore, we show that cell-cell communication re-establishes heterogeneous cell identities following the isolation of one cell type. The generation and maintenance of robust cell fate proportions is a new function for FGF signaling that may extend to other cell fate decisions.

Stem cells in stroke management

2010 ◽  
Vol 21 (2) ◽  
pp. 125-140
Author(s):  
Keith W Muir
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Tissue Regeneration ◽  
Clinical Studies ◽  
Cell Types ◽  
Adult Brain ◽  
Permanent Disability ◽  
Ischaemic Injury ◽  
Cell Therapies ◽  
The Brain

SummaryStem cells are a potential means of tissue regeneration in the brain that hold promise for treatment of the large number of stroke survivors who have permanent disability. Animal studies with stem cells derived from many different sources indicate that cells can migrate to the site of ischaemic injury in the brain, and that some survive and differentiate into neurones and glia with evidence of electrical function. Cells additionally promote endogenous repair mechanisms, including mobilization of neural stem cells resident within the adult brain. Whether the behavioural benefits seen with stem cell administration in rodent models reflect enhanced endogenous recovery or tissue regeneration is unclear. Production of stem cells to clinical standards and in quantities required for clinical studies is technically challenging. To date only a handful of patients have been involved in preliminary clinical studies of cell therapies for stroke, and there are therefore insufficient data to draw conclusions about either safety or efficacy. Further trials with several cell types are ongoing or planned, including neural stem cells, and bone marrow-derived stem cells and endothelial progenitor cells.

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