The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Bernhard Luscher - One of the best experts on this subject based on the ideXlab platform.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Yan Gu, Konstantinos Meletis, Josh Z Huang, Shaoyu Ge, Grigori Enikolopov, Karl Deisseroth, Bernhard LuscherAbstract:Parvalbumin-expressing interneurons regulate the activation and fate choice of adult neural stem Cells. The mammalian brain is capable of generating new nerve Cells into adulthood and has a number of specialized stem-Cell Niches for the purpose. Previous studies have examined the mechanisms that regulate the late stages of adult neurogenesis, but little is known about how quiescent neural stem Cells are regulated. Here, Juan Song and colleagues use genetic and optogenetic methods to demonstrate a role for parvalbumin-expressing (PV1) interneurons, but not other inhibitory neuron subtypes, in driving fate decisions for radial glia-like quiescent neural stem Cells in the adult mouse hippocampus. The study identifies a Niche Cell–signal–receptor trio and local circuits that provide a mechanism through which quiescent adult neural stem Cells can undergo activation and self-renewal in response to neuronal activity and experience. Adult neurogenesis arises from neural stem Cells within specialized Niches1,2,3. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival1,3. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells4,5,6,7,8,9 (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis9 of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division8. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Konstantinos Meletis, Josh Z Huang, Grigori Enikolopov, Karl Deisseroth, Gerald J Sun, Derek Hsu, Bernhard LuscherAbstract:Adult neurogenesis arises from neural stem Cells within specialized Niches. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
Stephen Dinardo - One of the best experts on this subject based on the ideXlab platform.
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Live imaging reveals hub Cell assembly and compaction dynamics during morphogenesis of the Drosophila testis Niche.
Developmental biology, 2018Co-Authors: Lauren Anllo, Lindsey W. Plasschaert, Justin Sui, Stephen DinardoAbstract:Abstract Adult stem Cells are often found in specialized Niches, where the constituent Cells direct self-renewal of their stem Cell pool. The Niche is therefore crucial for both normal homeostasis and tissue regeneration. In many mammalian tissues, Niche Cells have classically been difficult to identify, which has hampered any understanding of how tissues first construct Niches during development. Fortunately, the Drosophila germline stem Cell (GSC) Niche is well defined, allowing for unambiguous identification of both Niche Cells and resident stem Cells. The testis Niche first forms in the early embryo, during a late stage of gonadogenesis. Here, using live-imaging both in vivo and ex vivo, we follow pro-Niche Cells as they assemble and assume their final form. We show that after ex vivo culture the Niche appears fully functional, as judged by enrichment of adhesion proteins, the ability to activate STAT in adjacent GSCs, and to direct GSCs to divide orthogonally to the Niche, just as they would in situ. Collectively, our imaging has generated several novel insights on Niche morphogenesis that could not be inferred from fixed images alone. We identify dynamic processes that constitute an assembly phase and a compaction phase during morphogenesis. The compaction phase correlates with Cell neighbor exchange among the assembled pro-Niche Cells, as well as a burst of divisions among newly recruited stem Cells. Before compaction, an assembly phase involves the movement of pro-Niche Cells along the outer periphery of the gonad, using the extraCellular matrix (ECM) to assemble at the anterior of the gonad. Finally, live-imaging in integrin mutants allows us to define the role of pro-Niche Cell-ECM interaction with regard to the new assembly and compaction dynamics revealed here.
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Traffic jam functions in a branched pathway from Notch activation to Niche Cell fate
Development (Cambridge England), 2015Co-Authors: Lindsey Wingert, Stephen DinardoAbstract:The Niche directs key behaviors of its resident stem Cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide Niche specification and development. The male germline stem Cell Niche in Drosophila houses two stem Cell populations and is specified within the embryonic gonad, thus making it an exCellent model for studying Niche development. The hub Cells that form the Niche are specified early by Notch activation. Over the next few hours, these individual Cells then cluster together and take up a defined position before expressing markers of hub Cell differentiation. This timing suggests that there are other factors for Niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub Cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub Cells. Furthermore, Tj depletion is sufficient to generate ectopic hub Cells that can recruit stem Cells. Surprisingly, ectopic Niche Cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub Cell assembly in parallel to Tj downregulation.
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The endoderm specifies the mesodermal Niche for the germline in Drosophila via Delta-Notch signaling.
Development (Cambridge England), 2011Co-Authors: Tishina Okegbe, Stephen DinardoAbstract:Interactions between Niche Cells and stem Cells are vital for proper control over stem Cell self-renewal and differentiation. However, there are few tissues where the initial establishment of a Niche has been studied. The Drosophila testis houses two stem Cell populations, which each lie adjacent to somatic Niche Cells. Although these Niche Cells sustain spermatogenesis throughout life, it is not understood how their fate is established. Here, we show that Notch signaling is necessary to specify Niche Cell fate in the developing gonad. Surprisingly, our results indicate that adjacent endoderm is the source of the Notch-activating ligand Delta. We also find that Niche Cell specification occurs earlier than anticipated, well before the expression of extant markers for Niche Cell fate. This work further suggests that endoderm plays a dual role in germline development. The endoderm assists both in delivering germ Cells to the somatic gonadal mesoderm, and in specifying the Niche where these Cells will subsequently develop as stem Cells. Because in mammals primordial germ Cells also track through endoderm on their way to the genital ridge, our work raises the possibility that conserved mechanisms are employed to regulate germline Niche formation.
Grigori Enikolopov - One of the best experts on this subject based on the ideXlab platform.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Yan Gu, Konstantinos Meletis, Josh Z Huang, Shaoyu Ge, Grigori Enikolopov, Karl Deisseroth, Bernhard LuscherAbstract:Parvalbumin-expressing interneurons regulate the activation and fate choice of adult neural stem Cells. The mammalian brain is capable of generating new nerve Cells into adulthood and has a number of specialized stem-Cell Niches for the purpose. Previous studies have examined the mechanisms that regulate the late stages of adult neurogenesis, but little is known about how quiescent neural stem Cells are regulated. Here, Juan Song and colleagues use genetic and optogenetic methods to demonstrate a role for parvalbumin-expressing (PV1) interneurons, but not other inhibitory neuron subtypes, in driving fate decisions for radial glia-like quiescent neural stem Cells in the adult mouse hippocampus. The study identifies a Niche Cell–signal–receptor trio and local circuits that provide a mechanism through which quiescent adult neural stem Cells can undergo activation and self-renewal in response to neuronal activity and experience. Adult neurogenesis arises from neural stem Cells within specialized Niches1,2,3. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival1,3. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells4,5,6,7,8,9 (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis9 of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division8. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Konstantinos Meletis, Josh Z Huang, Grigori Enikolopov, Karl Deisseroth, Gerald J Sun, Derek Hsu, Bernhard LuscherAbstract:Adult neurogenesis arises from neural stem Cells within specialized Niches. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
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endothelial and perivascular Cells maintain haematopoietic stem Cells
Nature, 2012Co-Authors: Lei Ding, Grigori Enikolopov, Thomas L Saunders, Sean J MorrisonAbstract:Several Cell types have been proposed to create Niches for haematopoietic stem Cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate Niche Cell. Thus, the Cellular sources of these factors are undetermined. Stem Cell factor (SCF; also known as KITL) is a key Niche component that maintains HSCs. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular Cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic Cells, osteoblasts, nestin-cre- or nestin-creER-expressing Cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial Cells or leptin receptor (Lepr)-expressing perivascular stromal Cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular Cells. Thus, HSCs reside in a perivascular Niche in which multiple Cell types express factors that promote HSC maintenance.
Juan Song - One of the best experts on this subject based on the ideXlab platform.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Yan Gu, Konstantinos Meletis, Josh Z Huang, Shaoyu Ge, Grigori Enikolopov, Karl Deisseroth, Bernhard LuscherAbstract:Parvalbumin-expressing interneurons regulate the activation and fate choice of adult neural stem Cells. The mammalian brain is capable of generating new nerve Cells into adulthood and has a number of specialized stem-Cell Niches for the purpose. Previous studies have examined the mechanisms that regulate the late stages of adult neurogenesis, but little is known about how quiescent neural stem Cells are regulated. Here, Juan Song and colleagues use genetic and optogenetic methods to demonstrate a role for parvalbumin-expressing (PV1) interneurons, but not other inhibitory neuron subtypes, in driving fate decisions for radial glia-like quiescent neural stem Cells in the adult mouse hippocampus. The study identifies a Niche Cell–signal–receptor trio and local circuits that provide a mechanism through which quiescent adult neural stem Cells can undergo activation and self-renewal in response to neuronal activity and experience. Adult neurogenesis arises from neural stem Cells within specialized Niches1,2,3. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival1,3. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells4,5,6,7,8,9 (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis9 of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division8. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
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neuronal circuitry mechanism regulating adult quiescent neural stem Cell fate decision
Nature, 2012Co-Authors: Juan Song, Chun Zhong, Michael A Bonaguidi, Konstantinos Meletis, Josh Z Huang, Grigori Enikolopov, Karl Deisseroth, Gerald J Sun, Derek Hsu, Bernhard LuscherAbstract:Adult neurogenesis arises from neural stem Cells within specialized Niches. Neuronal activity and experience, presumably acting on this local Niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem Cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem Cells (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a Niche Cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem Cells in response to neuronal activity and experience.
Björn Schumacher - One of the best experts on this subject based on the ideXlab platform.
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Somatic Niche Cells Regulate the CEP-1/p53-Mediated DNA Damage Response in Primordial Germ Cells.
Developmental cell, 2019Co-Authors: Christine Kim, Simon Uszkoreit, Sara A. Wickström, Björn SchumacherAbstract:Summary Genome integrity in primordial germ Cells (PGCs) is a prerequisite for fertility and species maintenance. In C. elegans, PGCs require global-genome nucleotide excision repair (GG-NER) to remove UV-induced DNA lesions. Failure to remove the lesions leads to the activation of the C. elegans p53, CEP-1, resulting in mitotic arrest of the PGCs. We show that the eIF4E2 translation initiation factor IFE-4 in somatic gonad precursor (SGP) Niche Cells regulates the CEP-1/p53-mediated DNA damage response (DDR) in PGCs. We determine that the IFE-4 translation target EGL-15/FGFR regulates the non-Cell-autonomous DDR that is mediated via FGF-like signaling. Using hair follicle stem Cells as a paradigm, we demonstrate that the eIF4E2-mediated Niche Cell regulation of the p53 response in stem Cells is highly conserved in mammals. We thus reveal that the somatic Niche regulates the CEP-1/p53-mediated DNA damage checkpoint in PGCs. Our data suggest that the somatic Niche impacts the stability of heritable genomes.