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  1. Article ; Online: Generation of Mammalian Astrocyte Functional Heterogeneity.

    Bartels, Theresa / Rowitch, David H / Bayraktar, Omer Ali

    Cold Spring Harbor perspectives in biology

    2024  

    Abstract: Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development ... ...

    Abstract Mammalian astrocytes have regional roles within the brain parenchyma. Indeed, the notion that astrocytes are molecularly heterogeneous could help explain how the central nervous system (CNS) retains embryonic positional information through development into specialized regions into adulthood. A growing body of evidence supports the concept of morphological and molecular differences between astrocytes in different brain regions, which might relate to their derivation from regionally patterned radial glia and/or local neuron inductive cues. Here, we review evidence for regionally encoded functions of astrocytes to provide an integrated concept on lineage origins and heterogeneity to understand regional brain organization, as well as emerging technologies to identify and further investigate novel roles for astrocytes.
    Language English
    Publishing date 2024-05-01
    Publishing country United States
    Document type Journal Article
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a041351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Diversity and Function of Glial Cell Types in Multiple Sclerosis.

    Schirmer, Lucas / Schafer, Dorothy P / Bartels, Theresa / Rowitch, David H / Calabresi, Peter A

    Trends in immunology

    2021  Volume 42, Issue 3, Page(s) 228–247

    Abstract: Glial subtype diversity is an emerging topic in neurobiology and immune-mediated neurological diseases such as multiple sclerosis (MS). We discuss recent conceptual and technological advances that allow a better understanding of the transcriptomic and ... ...

    Abstract Glial subtype diversity is an emerging topic in neurobiology and immune-mediated neurological diseases such as multiple sclerosis (MS). We discuss recent conceptual and technological advances that allow a better understanding of the transcriptomic and functional heterogeneity of oligodendrocytes (OLs), astrocytes, and microglial cells under inflammatory-demyelinating conditions. Recent single cell transcriptomic studies suggest the occurrence of novel homeostatic and reactive glial subtypes and provide insight into the molecular events during disease progression. Multiplexed RNA in situ hybridization has enabled 'mapping back' dysregulated gene expression to glial subtypes within the MS lesion microenvironment. These findings suggest novel homeostatic and reactive glial-cell-type functions both in immune-related processes and neuroprotection relevant to understanding the pathology of MS.
    MeSH term(s) Astrocytes ; Humans ; Microglia ; Multiple Sclerosis ; Neuroglia ; Oligodendroglia
    Language English
    Publishing date 2021-02-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2021.01.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1601: 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)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 2: Show issues

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  3. Article ; Online: The fatty acid binding protein FABP7 is required for optimal oligodendrocyte differentiation during myelination but not during remyelination.

    Foerster, Sarah / Guzman de la Fuente, Alerie / Kagawa, Yoshiteru / Bartels, Theresa / Owada, Yuji / Franklin, Robin J M

    Glia

    2020  Volume 68, Issue 7, Page(s) 1410–1420

    Abstract: The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one ... ...

    Abstract The major constituents of the myelin sheath are lipids, which are made up of fatty acids (FAs). The hydrophilic environment inside the cells requires FAs to be bound to proteins, preventing their aggregation. Fatty acid binding proteins (FABPs) are one class of proteins known to bind FAs in a cell. Given the crucial role of FAs for myelin sheath formation we investigated the role of FABP7, the major isoform expressed in oligodendrocyte progenitor cells (OPCs), in developmental myelination and remyelination. Here, we show that the knockdown of Fabp7 resulted in a reduction of OPC differentiation in vitro. Consistent with this result, a delay in developmental myelination was observed in Fabp7 knockout animals. This delay was transient with full myelination being established before adulthood. FABP7 was dispensable for remyelination, as the knockout of Fapb7 did not alter remyelination efficiency in a focal demyelination model. In summary, while FABP7 is important in OPC differentiation in vitro, its function is not crucial for myelination and remyelination in vivo.
    MeSH term(s) Animals ; Cell Differentiation/physiology ; Demyelinating Diseases/metabolism ; Fatty Acid-Binding Proteins/metabolism ; Myelin Sheath/metabolism ; Oligodendrocyte Precursor Cells/metabolism ; Oligodendroglia/metabolism ; Remyelination/physiology ; Stem Cells/metabolism
    Chemical Substances Fatty Acid-Binding Proteins
    Language English
    Publishing date 2020-02-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639414-0
    ISSN 1098-1136 ; 0894-1491
    ISSN (online) 1098-1136
    ISSN 0894-1491
    DOI 10.1002/glia.23789
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2345: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map.

    Bayraktar, Omer Ali / Bartels, Theresa / Holmqvist, Staffan / Kleshchevnikov, Vitalii / Martirosyan, Araks / Polioudakis, Damon / Ben Haim, Lucile / Young, Adam M H / Batiuk, Mykhailo Y / Prakash, Kirti / Brown, Alexander / Roberts, Kenny / Paredes, Mercedes F / Kawaguchi, Riki / Stockley, John H / Sabeur, Khalida / Chang, Sandra M / Huang, Eric / Hutchinson, Peter /
    Ullian, Erik M / Hemberg, Martin / Coppola, Giovanni / Holt, Matthew G / Geschwind, Daniel H / Rowitch, David H

    Nature neuroscience

    2020  Volume 23, Issue 4, Page(s) 500–509

    Abstract: Although the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells show distinct layering. In the present study, we developed a high-content pipeline, the large-area spatial transcriptomic (LaST) map, which ... ...

    Abstract Although the cerebral cortex is organized into six excitatory neuronal layers, it is unclear whether glial cells show distinct layering. In the present study, we developed a high-content pipeline, the large-area spatial transcriptomic (LaST) map, which can quantify single-cell gene expression in situ. Screening 46 candidate genes for astrocyte diversity across the mouse cortex, we identified superficial, mid and deep astrocyte identities in gradient layer patterns that were distinct from those of neurons. Astrocyte layer features, established in the early postnatal cortex, mostly persisted in adult mouse and human cortex. Single-cell RNA sequencing and spatial reconstruction analysis further confirmed the presence of astrocyte layers in the adult cortex. Satb2 and Reeler mutations that shifted neuronal post-mitotic development were sufficient to alter glial layering, indicating an instructive role for neuronal cues. Finally, astrocyte layer patterns diverged between mouse cortical regions. These findings indicate that excitatory neurons and astrocytes are organized into distinct lineage-associated laminae.
    MeSH term(s) Animals ; Astrocytes/cytology ; Astrocytes/metabolism ; Brain Mapping ; Cerebral Cortex/cytology ; Cerebral Cortex/metabolism ; Humans ; Mice ; Neurons/cytology ; Neurons/metabolism ; Transcriptome
    Language English
    Publishing date 2020-03-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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/s41593-020-0602-1
    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:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 67: Show issues

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  5. Article ; Online: Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis.

    Kirwan, Peter / Kay, Richard G / Brouwers, Bas / Herranz-Pérez, Vicente / Jura, Magdalena / Larraufie, Pierre / Jerber, Julie / Pembroke, Jason / Bartels, Theresa / White, Anne / Gribble, Fiona M / Reimann, Frank / Farooqi, I Sadaf / O'Rahilly, Stephen / Merkle, Florian T

    Molecular metabolism

    2018  Volume 17, Page(s) 82–97

    Abstract: Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC ... ...

    Abstract Objective: The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated.
    Methods: We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from human pluripotent stem cells (hPSCs) using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the sequence and quantify the production of hypothalamic neuropeptides, including those derived from POMC.
    Results: In both in vitro and in vivo hypothalamic cells, LC-MS/MS revealed the sequence of hundreds of neuropeptides as a resource for the field. Although the existence of β-melanocyte stimulating hormone (MSH) is controversial, we found that both this peptide and desacetyl α-MSH (d-α-MSH) were produced in considerable excess of acetylated α-MSH. In hPSC-derived hypothalamic neurons, these POMC derivatives were appropriately trafficked, secreted, and their production was significantly (P < 0.0001) increased in response to the hormone leptin.
    Conclusions: Our findings challenge the assumed pre-eminence of α-MSH and suggest that in humans, d-α-MSH and β-MSH are likely to be the predominant physiological products acting on melanocortin receptors.
    MeSH term(s) Chromatography, Liquid ; Female ; Homeostasis/physiology ; Humans ; Hypothalamus ; Leptin/metabolism ; Male ; Mass Spectrometry/methods ; Melanocortins/metabolism ; Neurons/metabolism ; Neuropeptides/metabolism ; Pluripotent Stem Cells/metabolism ; Pro-Opiomelanocortin/metabolism ; Receptors, Melanocortin/metabolism ; Tandem Mass Spectrometry ; alpha-MSH/metabolism ; beta-MSH/metabolism
    Chemical Substances Leptin ; Melanocortins ; Neuropeptides ; Receptors, Melanocortin ; beta-MSH ; alpha-MSH (581-05-5) ; Pro-Opiomelanocortin (66796-54-1)
    Language English
    Publishing date 2018-08-21
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2708735-9
    ISSN 2212-8778 ; 2212-8778
    ISSN (online) 2212-8778
    ISSN 2212-8778
    DOI 10.1016/j.molmet.2018.08.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.

    Khurana, Vikram / Peng, Jian / Chung, Chee Yeun / Auluck, Pavan K / Fanning, Saranna / Tardiff, Daniel F / Bartels, Theresa / Koeva, Martina / Eichhorn, Stephen W / Benyamini, Hadar / Lou, Yali / Nutter-Upham, Andy / Baru, Valeriya / Freyzon, Yelena / Tuncbag, Nurcan / Costanzo, Michael / San Luis, Bryan-Joseph / Schöndorf, David C / Barrasa, M Inmaculada /
    Ehsani, Sepehr / Sanjana, Neville / Zhong, Quan / Gasser, Thomas / Bartel, David P / Vidal, Marc / Deleidi, Michela / Boone, Charles / Fraenkel, Ernest / Berger, Bonnie / Lindquist, Susan

    Cell systems

    2017  Volume 4, Issue 2, Page(s) 157–170.e14

    Abstract: Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein ... ...

    Abstract Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To "humanize" this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy.
    MeSH term(s) Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Ataxin-2/chemistry ; Ataxin-2/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Disease Susceptibility ; Endoplasmic Reticulum/metabolism ; Eukaryotic Initiation Factor-4G/chemistry ; Eukaryotic Initiation Factor-4G/metabolism ; Gene Regulatory Networks/genetics ; Genome, Fungal ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Neurons/cytology ; Neurons/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
    Chemical Substances Amyloid beta-Peptides ; Ataxin-2 ; DNA-Binding Proteins ; EIF4G1 protein, human ; Eukaryotic Initiation Factor-4G ; TARDBP protein, human ; alpha-Synuclein
    Language English
    Publishing date 2017-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2016.12.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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