Tramtrack controls glial number and identity in the Drosophila embryonic CNS

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 4093-4101 ◽  
Author(s):  
Paul Badenhorst
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
System Analysis ◽  
Cell Formation ◽  
S Phase ◽  
Dependent Manner ◽  
Multipotent Stem Cells ◽  
Protein Levels ◽  
Cycle Dependent

Neurons and glia are often derived from common multipotent stem cells. In Drosophila, neural identity appears to be the default fate of these precursors. Stem cells that generate either neurons or glia transiently express neural stem cell-specific markers. Further development as glia requires the activation of glial-specific regulators. However, this must be accompanied by simultaneous repression of the alternate neural fate. I show that the Drosophila transcriptional repressor Tramtrack is a key repressor of neuronal fates. It is expressed at high levels in all mature glia of the embryonic central nervous system. Analysis of the temporal profile of Tramtrack expression in glia shows that it follows that of existing glial markers. When expressed ectopically before neural stem cell formation, Tramtrack represses the neural stem cell-specific genes asense and deadpan. Surprisingly, Tramtrack protein levels oscillate in a cell cycle-dependent manner in proliferating glia, with expression dropping before replication, but re-initiating after S phase. Overexpression of Tramtrack blocks glial development by inhibiting S-phase and repressing expression of the S-phase cyclin, cyclin E. Conversely, in tramtrack mutant embryos, glia are disrupted and undergo additional rounds of replication. I propose that Tramtrack ensures stable mature glial identity by both repressing neuroblast-specific genes and controlling glial cell proliferation.

Control of nerve cell formation from multipotent stem cells in Hydra

1979 ◽  
Vol 40 (1) ◽  
pp. 193-205 ◽  
Author(s):  
S. Berking
Keyword(s):  
Stem Cells ◽  
Nerve Cell ◽  
Cell Formation ◽  
S Phase ◽  
Nerve Cells ◽  
Endogenous Inhibitor ◽  
Multipotent Stem Cells ◽  
Low Concentrations ◽  
Short Signal ◽  
Time Of Feeding

Feeding of starved animals provides a very short signal which determines stem cells to differentiate into nerve cells after the next mitosis. Only those stem cells become determined which are just in the middle of their S-phase at the time of feeding. Stem cells of any other stage of the cycle do not become determined. Nerve cell determination is suppressed by very low concentrations of an endogenous inhibitor. The inhibitor exerts its effect only during the first half of the S-phase, not before and not after this period. Based on these finding it is proposed that stem cells are susceptible to 2 different signals during the first half of their S-phase; one signal allows the development into nerve cells, the other prevents this development. Within this period the decision whether to become a nerve cell or not is reversible. It becomes fixed at the end of this period.

scholarly journals Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

2019 ◽  
Author(s):  
Tamsin J. Samuels ◽  
Aino I. Järvelin ◽  
David Ish-Horowicz ◽  
Ilan Davis
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Mrna Stability ◽  
Rna Binding ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Protein Levels ◽  
The Brain

ABSTRACTThe numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by known extrinsic signals. However, the intrinsic mechanisms that control the characteristic proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, while heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.Abstract Figure

scholarly journals Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tamsin J Samuels ◽  
Aino I Järvelin ◽  
David Ish-Horowicz ◽  
Ilan Davis
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Mrna Stability ◽  
Rna Binding ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
Protein Levels ◽  
The Brain

The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by important known stem cell-extrinsic signals. However, the cell-intrinsic mechanisms that control the distinctive proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, and heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.

scholarly journals Nuclear Export of Smads by RanBP3L Regulates Bone Morphogenetic Protein Signaling and Mesenchymal Stem Cell Differentiation

2015 ◽  
Vol 35 (10) ◽  
pp. 1700-1711 ◽  
Author(s):  
Fenfang Chen ◽  
Xia Lin ◽  
Pinglong Xu ◽  
Zhengmao Zhang ◽  
Yanzhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Mesenchymal Stem Cell ◽  
Nuclear Export ◽  
Stem Cell Differentiation ◽  
Bmp Signaling ◽  
Dependent Manner ◽  
Mesenchymal Stem Cell Differentiation

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance and differentiation. BMPs can induce osteogenesis and inhibit myogenesis of mesenchymal stem cells. Canonical BMP signaling is stringently controlled through reversible phosphorylation and nucleocytoplasmic shuttling of Smad1, Smad5, and Smad8 (Smad1/5/8). However, how the nuclear export of Smad1/5/8 is regulated remains unclear. Here we report that the Ran-binding protein RanBP3L acts as a nuclear export factor for Smad1/5/8. RanBP3L directly recognizes dephosphorylated Smad1/5/8 and mediates their nuclear export in a Ran-dependent manner. Increased expression of RanBP3L blocks BMP-induced osteogenesis of mouse bone marrow-derived mesenchymal stem cells and promotes myogenic induction of C2C12 mouse myoblasts, whereas depletion of RanBP3L expression enhances BMP-dependent stem cell differentiation activity and transcriptional responses. In conclusion, our results demonstrate that RanBP3L, as a nuclear exporter for BMP-specific Smads, plays a critical role in terminating BMP signaling and regulating mesenchymal stem cell differentiation.

Biomaterials Nano Geometry for Control of Stem Cell Differentiation

2009 ◽  
Vol 1239 ◽  
Author(s):  
Karla Brammer ◽  
Seunghan Oh ◽  
Sungho Jin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Differentiation ◽  
Human Mesenchymal Stem Cell ◽  
Oxide Surface ◽  
Specific Cell ◽  
Implant Surface ◽  
Multipotent Stem Cells

AbstractTwo important goals in stem cell research are to control the cell proliferation without differentiation, and also to direct the differentiation into a specific cell lineage when desired. Recent studies indicate that the nanostructures substantially influence the stem cell behavior. It is well known that mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into stromal lineages such as adipocyte, chondrocyte, fibroblast, myocyte, and osteoblast cell types. By examining the cellular behavior of MSCs cultured in vitro on nanostructures, some understanding of the effects that the nanostructures have on the stem cell’s response has been obtained. Here we demonstrate that TiO2 nanotubes produced by anodization on Ti implant surface can regulate human mesenchymal stem cell (hMSC) differentiation towards an osteoblast lineage in the absence of osteogenic inducing factors. Altering the dimensions of nanotubular-shaped titanium oxide surface structures independently allowed either augmented human mesenchymal stem cell (hMSC) adhesion at smaller diameter levels or a specific differentiation of hMSCs into osteoblasts using only the geometric cues. Small (˜30 nm diameter) nanotubes promoted adhesion without noticeable differentiation, while larger (˜70 - 100 nm diameter) nanotubes elicited a dramatic, ˜10 fold stem cell elongation, which induced cytoskeletal stress and selective differentiation into osteoblast-like cells, offering a promising nanotechnology-based route for novel orthopaedics-related hMSC treatments. The fact that a guided and preferential osteogenic differentiation of stem cells can be achieved using substrate nanotopography alone without using potentially toxic, differentiation-inducing chemical agents is significant, which can be useful for future development of novel and enhanced stem cell control and therapeutic implant development.

scholarly journals Wnt5a Signaling in Normal and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Zhou ◽  
Thomas J. Kipps ◽  
Suping Zhang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Target Cells ◽  
Dependent Manner ◽  
Self Renewal ◽  
Surface Receptors ◽  
Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

scholarly journals Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Stem Cell Marker ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

scholarly journals Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

2020 ◽  
Author(s):  
JE Le Belle ◽  
J Sperry ◽  
K Ludwig ◽  
NG Harris ◽  
MA Caldwell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Olfactory Bulb ◽  
Neural Stem Cells ◽  
Egf Receptor ◽  
Brain Repair ◽  
Multipotent Stem Cells ◽  
Growth And Survival

AbstractFatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair.Significance StatementWe have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.

scholarly journals Contribution of Resident Stem Cells to Liver and Biliary Tree Regeneration in Human Diseases

2018 ◽  
Vol 19 (10) ◽  
pp. 2917 ◽  
Author(s):  
Diletta Overi ◽  
Guido Carpino ◽  
Vincenzo Cardinale ◽  
Antonio Franchitto ◽  
Samira Safarikia ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Human Liver ◽  
Progenitor Cell ◽  
Biliary Tree ◽  
Tree Regeneration ◽  
Multipotent Stem Cells ◽  
Resident Stem Cells ◽  
Stem Cell Niches

Two distinct stem/progenitor cell populations of biliary origin have been identified in the adult liver and biliary tree. Hepatic Stem/progenitor Cells (HpSCs) are bipotent progenitor cells located within the canals of Hering and can be differentiated into mature hepatocytes and cholangiocytes; Biliary Tree Stem/progenitor Cells (BTSCs) are multipotent stem cells located within the peribiliary glands of large intrahepatic and extrahepatic bile ducts and able to differentiate into hepatic and pancreatic lineages. HpSCs and BTSCs are endowed in a specialized niche constituted by supporting cells and extracellular matrix compounds. The actual contribution of these stem cell niches to liver and biliary tree homeostatic regeneration is marginal; this is due to the high replicative capabilities and plasticity of mature parenchymal cells (i.e., hepatocytes and cholangiocytes). However, the study of human liver and biliary diseases disclosed how these stem cell niches are involved in the regenerative response after extensive and/or chronic injuries, with the activation of specific signaling pathways. The present review summarizes the contribution of stem/progenitor cell niches in human liver diseases, underlining mechanisms of activation and clinical implications, including fibrogenesis and disease progression.

EVALUATION OF HERBAL EXTRACTS SYNERGISTIC ACTIVITY USING TISSUE STEM CELLS

INDIAN DRUGS ◽  
2017 ◽  
Vol 54 (02) ◽  
pp. 73-75
Author(s):  
S. Priya ◽  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
System Analysis ◽  
Cultured Cells ◽  
Well Being ◽  
Ocimum Sanctum ◽  
Synergistic Activity ◽  
Stem Cell Proliferation ◽  
Cell Proliferation And Differentiation

Herbal stem cell therapy promotes endogenous stem cell proliferation and differentiation and is ued in the treatment of various human diseases. At present, recommendations are warranted to support the consumption of foods rich in bioactive components. Stem cells and progenitor cells from organs form the basis for well-being of the mammalian system. Analysis based on these cultured cells would form a viable alternative to stem cell transplantation, and would facilitate to design approaches that stimulate endogenous stem cells through diet to promote healing and regeneration. In the present study, synergistic activity of selected herbs such as Phyllanthus amarus, Myristica fragrans, Ocimum sanctum and Withania somnifera were analysed for their stem cell proliferation enhancing activity using goat bone marrow derived stem cells.

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