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  1. Article: TIMP3 promotes the maintenance of neural stem-progenitor cells in the mouse subventricular zone.

    Fang, Lingyan / Kuniya, Takaaki / Harada, Yujin / Yasuda, Osamu / Maeda, Nobuyo / Suzuki, Yutaka / Kawaguchi, Daichi / Gotoh, Yukiko

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1149603

    Abstract: Adult neural stem cells (NSCs) in the mouse subventricular zone (SVZ) serve as a lifelong reservoir for newborn olfactory bulb neurons. Recent studies have identified a slowly dividing subpopulation of embryonic neural stem-progenitor cells (NPCs) as the ...

    Abstract Adult neural stem cells (NSCs) in the mouse subventricular zone (SVZ) serve as a lifelong reservoir for newborn olfactory bulb neurons. Recent studies have identified a slowly dividing subpopulation of embryonic neural stem-progenitor cells (NPCs) as the embryonic origin of adult NSCs. Yet, little is known about how these slowly dividing embryonic NPCs are maintained until adulthood while other NPCs are extinguished by the completion of brain development. The extracellular matrix (ECM) is an essential component of stem cell niches and thus a key determinant of stem cell fate. Here we investigated tissue inhibitors of metalloproteinases (TIMPs)-regulators of ECM remodeling-for their potential roles in the establishment of adult NSCs. We found that
    Language English
    Publishing date 2023-06-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1149603
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: [Establishment and Maintenance of Adult Neural Stem Cells].

    Yuizumi, Naoya / Harada, Yujin

    Brain and nerve = Shinkei kenkyu no shinpo

    2017  Volume 69, Issue 9, Page(s) 1027–1034

    Abstract: Neural stem cells (NSCs) in the adult mammalian brain produce new neurons throughout life. Defects in adult neurogenesis can influence neurodegenerative and psychiatric disorders. Hence, understanding long-term maintenance of adult NSCs is crucial. Cell- ... ...

    Abstract Neural stem cells (NSCs) in the adult mammalian brain produce new neurons throughout life. Defects in adult neurogenesis can influence neurodegenerative and psychiatric disorders. Hence, understanding long-term maintenance of adult NSCs is crucial. Cell-intrinsic and -extrinsic factors contribute to long-term maintenance of adult NSCs, and we have previously reported that NSCs produce their own niches that send a feedback signal for their own maintenance. In addition, we have identified a slowly dividing subpopulation of embryonic neural progenitor cells that is set aside during development, and later becomes a substantial fraction of NSCs in the adult subventricular zone. Here, we review the mechanisms of long-term maintenance and embryonic origin of adult NSCs. We also discuss current topics on adult NSCs and future perspectives in this field of study.
    Language Japanese
    Publishing date 2017-09
    Publishing country Japan
    Document type English Abstract ; Journal Article
    ZDB-ID 390389-8
    ISSN 1344-8129 ; 1881-6096 ; 0006-8969
    ISSN (online) 1344-8129
    ISSN 1881-6096 ; 0006-8969
    DOI 10.11477/mf.1416200862
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 398: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  3. Article: Genetic mapping identifies Homer1 as a developmental modifier of attention.

    Gershon, Zachary / Bonito-Oliva, Alessandra / Kanke, Matt / Terceros, Andrea / Rankin, Genelle / Fak, John / Harada, Yujin / Iannone, Andrew F / Gebremedhin, Millennium / Fabella, Brian / De Marco Garcia, Natalia V / Sethupathy, Praveen / Rajasethupathy, Priya

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Attention is required for most higher-order cognitive functions. Prior studies have revealed functional roles for the prefrontal cortex and its extended circuits to enabling attention, but the underlying molecular processes and their impacts on cellular ... ...

    Abstract Attention is required for most higher-order cognitive functions. Prior studies have revealed functional roles for the prefrontal cortex and its extended circuits to enabling attention, but the underlying molecular processes and their impacts on cellular and circuit function remain poorly understood. To develop insights, we here took an unbiased forward genetics approach to identify single genes of large effect on attention. We studied 200 genetically diverse mice on measures of pre-attentive processing and through genetic mapping identified a small locus on chromosome 13 (95%CI: 92.22-94.09 Mb) driving substantial variation (19%) in this trait. Further characterization of the locus revealed a causative gene, Homer1, encoding a synaptic protein, where down-regulation of its short isoforms in prefrontal cortex (PFC) during early postnatal development led to improvements in multiple measures of attention in the adult. Subsequent mechanistic studies revealed that prefrontal
    Language English
    Publishing date 2024-02-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.17.533136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: BMP signaling suppresses Gemc1 expression and ependymal differentiation of mouse telencephalic progenitors.

    Omiya, Hanae / Yamaguchi, Shima / Watanabe, Tomoyuki / Kuniya, Takaaki / Harada, Yujin / Kawaguchi, Daichi / Gotoh, Yukiko

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 613

    Abstract: The lateral ventricles of the adult mammalian brain are lined by a single layer of multiciliated ependymal cells, which generate a flow of cerebrospinal fluid through directional beating of their cilia as well as regulate neurogenesis through interaction ...

    Abstract The lateral ventricles of the adult mammalian brain are lined by a single layer of multiciliated ependymal cells, which generate a flow of cerebrospinal fluid through directional beating of their cilia as well as regulate neurogenesis through interaction with adult neural stem cells. Ependymal cells are derived from a subset of embryonic neural stem-progenitor cells (NPCs, also known as radial glial cells) that becomes postmitotic during the late embryonic stage of development. Members of the Geminin family of transcriptional regulators including GemC1 and Mcidas play key roles in the differentiation of ependymal cells, but it remains largely unclear what extracellular signals regulate these factors and ependymal differentiation during embryonic and early-postnatal development. We now show that the levels of Smad1/5/8 phosphorylation and Id1/4 protein expression-both of which are downstream events of bone morphogenetic protein (BMP) signaling-decline in cells of the ventricular-subventricular zone in the mouse lateral ganglionic eminence in association with ependymal differentiation. Exposure of postnatal NPC cultures to BMP ligands or to a BMP receptor inhibitor suppressed and promoted the emergence of multiciliated ependymal cells, respectively. Moreover, treatment of embryonic NPC cultures with BMP ligands reduced the expression level of the ependymal marker Foxj1 and suppressed the emergence of ependymal-like cells. Finally, BMP ligands reduced the expression levels of Gemc1 and Mcidas in postnatal NPC cultures, whereas the BMP receptor inhibitor increased them. Our results thus implicate BMP signaling in suppression of ependymal differentiation from NPCs through regulation of Gemc1 and Mcidas expression during embryonic and early-postnatal stages of mouse telencephalic development.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/metabolism ; Cell Cycle Proteins/antagonists & inhibitors ; Cell Cycle Proteins/metabolism ; Cell Differentiation ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Ependyma/cytology ; Ependyma/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis ; Telencephalon/cytology ; Telencephalon/metabolism
    Chemical Substances Bone Morphogenetic Proteins ; Cell Cycle Proteins ; Gmnc protein, mouse
    Language English
    Publishing date 2021-01-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-79610-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cell cycle arrest determines adult neural stem cell ontogeny by an embryonic Notch-nonoscillatory Hey1 module.

    Harada, Yujin / Yamada, Mayumi / Imayoshi, Itaru / Kageyama, Ryoichiro / Suzuki, Yutaka / Kuniya, Takaaki / Furutachi, Shohei / Kawaguchi, Daichi / Gotoh, Yukiko

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 6562

    Abstract: Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a subpopulation of embryonic neural stem-progenitor cells ( ... ...

    Abstract Quiescent neural stem cells (NSCs) in the adult mouse brain are the source of neurogenesis that regulates innate and adaptive behaviors. Adult NSCs in the subventricular zone are derived from a subpopulation of embryonic neural stem-progenitor cells (NPCs) that is characterized by a slower cell cycle relative to the more abundant rapid cycling NPCs that build the brain. Yet, how slow cell cycle can cause the establishment of adult NSCs remains largely unknown. Here, we demonstrate that Notch and an effector Hey1 form a module that is upregulated by cell cycle arrest in slowly dividing NPCs. In contrast to the oscillatory expression of the Notch effectors Hes1 and Hes5 in fast cycling progenitors, Hey1 displays a non-oscillatory stationary expression pattern and contributes to the long-term maintenance of NSCs. These findings reveal a novel division of labor in Notch effectors where cell cycle rate biases effector selection and cell fate.
    MeSH term(s) Adult Stem Cells/metabolism ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Brain/cytology ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cell Cycle Checkpoints/genetics ; Cell Cycle Checkpoints/physiology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Embryonic Stem Cells ; Gene Expression ; Lateral Ventricles/metabolism ; Mice ; Nervous System ; Neurogenesis/genetics ; Neurogenesis/physiology ; Receptor, Notch1 ; Repressor Proteins/metabolism
    Chemical Substances Basic Helix-Loop-Helix Transcription Factors ; Cell Cycle Proteins ; Hes5 protein, mouse ; Hey1 protein, mouse ; Notch1 protein, mouse ; Receptor, Notch1 ; Repressor Proteins
    Language English
    Publishing date 2021-11-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-26605-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Maintenance of neural stem-progenitor cells by the lysosomal biosynthesis regulators TFEB and TFE3 in the embryonic mouse telencephalon.

    Yuizumi, Naoya / Harada, Yujin / Kuniya, Takaaki / Sunabori, Takehiko / Koike, Masato / Wakabayashi, Masaki / Ishihama, Yasushi / Suzuki, Yutaka / Kawaguchi, Daichi / Gotoh, Yukiko

    Stem cells (Dayton, Ohio)

    2021  Volume 39, Issue 7, Page(s) 929–944

    Abstract: Lysosomes have recently been implicated in regulation of quiescence in adult neural stem cells (NSCs). Whether lysosomes regulate the differentiation of neural stem-progenitor cells (NPCs) in the embryonic brain has remained unknown, however. We here ... ...

    Abstract Lysosomes have recently been implicated in regulation of quiescence in adult neural stem cells (NSCs). Whether lysosomes regulate the differentiation of neural stem-progenitor cells (NPCs) in the embryonic brain has remained unknown, however. We here show that lysosomes are more abundant in rapidly dividing NPCs than in differentiating neurons in the embryonic mouse neocortex and ganglionic eminence. The genes for TFEB and TFE3, master regulators of lysosomal biosynthesis, as well as other lysosome-related genes were also expressed at higher levels in NPCs than in differentiating neurons. Anatomic analysis revealed accumulation of lysosomes at the apical and basal endfeet of NPCs. Knockdown of TFEB and TFE3, or that of the lysosomal transporter Slc15a4, resulted in premature differentiation of neocortical NPCs. Conversely, forced expression of an active form of TFEB (TFEB-AA) suppressed neuronal differentiation of NPCs in association with upregulation of NPC-related genes. These results together point to a previously unappreciated role for TFEB and TFE3, and possibly for lysosomes, in maintenance of the undifferentiated state of embryonic NPCs. We further found that lysosomes are even more abundant in an NPC subpopulation that rarely divides and includes the embryonic origin of adult NSCs than in the majority of NPCs that divide frequently for construction of the embryonic brain, and that overexpression of TFEB-AA also suppressed the cell cycle of neocortical NPCs. Our results thus also implicate lysosomes in establishment of the slowly dividing, embryonic origin of adult NSCs.
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Cell Differentiation/physiology ; Lysosomes/metabolism ; Membrane Transport Proteins/metabolism ; Mice ; Neocortex ; Neural Stem Cells/metabolism
    Chemical Substances Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Membrane Transport Proteins ; Slc15a4 protein, mouse ; Tcfeb protein, mouse ; Tcfe3 protein, mouse (136896-33-8)
    Language English
    Publishing date 2021-03-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.3359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1894: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  7. Article ; Online: Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells.

    Furutachi, Shohei / Miya, Hiroaki / Watanabe, Tomoyuki / Kawai, Hiroki / Yamasaki, Norihiko / Harada, Yujin / Imayoshi, Itaru / Nelson, Mark / Nakayama, Keiichi I / Hirabayashi, Yusuke / Gotoh, Yukiko

    Nature neuroscience

    2015  Volume 18, Issue 5, Page(s) 657–665

    Abstract: The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse ... ...

    Abstract The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.
    MeSH term(s) Animals ; Cell Cycle ; Cell Division ; Cell Lineage ; Cyclin-Dependent Kinase Inhibitor p57/biosynthesis ; Cyclin-Dependent Kinase Inhibitor p57/genetics ; Cyclin-Dependent Kinase Inhibitor p57/physiology ; Genes, Reporter ; Histones/biosynthesis ; Histones/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Nerve Tissue Proteins/biosynthesis ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/physiology ; Neural Stem Cells/cytology ; Neurogenesis ; Recombinant Fusion Proteins/metabolism ; Telencephalon/cytology ; Telencephalon/embryology
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p57 ; Histones ; Nerve Tissue Proteins ; Recombinant Fusion Proteins
    Language English
    Publishing date 2015-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/nn.3989
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4891: Show issues Location:
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    Zs.MG 67: Show issues

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