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  1. Article ; Online: Sulfation of Glycosaminoglycans Modulates the Cell Cycle of Embryonic Mouse Spinal Cord Neural Stem Cells

    Elena Schaberg / Ursula Theocharidis / Marcus May / Katrin Lessmann / Timm Schroeder / Andreas Faissner

    Frontiers in Cell and Developmental Biology, Vol

    2021  Volume 9

    Abstract: In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of ... ...

    Abstract In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of receptor protein tyrosine phosphatase-beta/zeta (RPTPβ/ζ), a trans-membrane receptor expressed by NSPCs. The chondroitin sulfate glycosaminoglycan chains are sulfated at distinct positions by sulfotransferases, thereby generating the distinct DSD-1-epitope that is recognized by the monoclonal antibody (mAb) 473HD. We detected the epitope, the critical enzymes and RPTPβ/ζ in the developing spinal cord. To obtain insight into potential biological functions, we exposed spinal cord NSPCs to sodium chlorate. The reagent suppresses the sulfation of glycosaminoglycans, thereby erasing any sulfation code expressed by the glycosaminoglycan polymers. When NSPCs were treated with chlorate and cultivated in the presence of FGF2, their proliferation rate was clearly reduced, while NSPCs exposed to EGF were less affected. Time-lapse video microscopy and subsequent single-cell tracking revealed that pedigrees of NSPCs cultivated with FGF2 were strongly disrupted when sulfation was suppressed. Furthermore, the NSPCs displayed a protracted cell cycle length. We conclude that the inhibition of sulfation with sodium chlorate interferes with the FGF2-dependent cell cycle progression in spinal cord NSPCs.
    Keywords chondroitin sulfate proteoglycan ; extracellular matrix ; single-cell tracking ; spinal cord ; sodium chlorate ; sulfation ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Cell tracking in vitro reveals that the extracellular matrix glycoprotein Tenascin-C modulates cell cycle length and differentiation in neural stem/progenitor cells of the developing mouse spinal cord

    Marcus May / Bernd Denecke / Timm Schroeder / Magdalena Götz / Andreas Faissner

    Biology Open, Vol 7, Iss

    2018  Volume 7

    Abstract: Generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Previously, we have shown that the glycoprotein of the extracellular matrix (ECM) tenascin-C (Tnc) modulates the expression territories of the patterning ... ...

    Abstract Generation of astrocytes during the development of the mammalian spinal cord is poorly understood. Previously, we have shown that the glycoprotein of the extracellular matrix (ECM) tenascin-C (Tnc) modulates the expression territories of the patterning genes Nkx6.1 and Nkx2.2 in the developing ventral spinal cord, tunes the responsiveness of neural stem/progenitor cells towards the cytokines FGF2 and EGF and thereby promotes astrocyte maturation. In order to obtain further mechanistic insight into these processes, we have compared embryonic day-15 spinal cord neural progenitor cells (NPCs) from wild-type and Tnc knockout mice using continuous single-cell live imaging and cell lineage analysis in vitro. Tnc knockout cells displayed a significantly reduced rate of cell division both in response to FGF2 and EGF. When individual clones of dividing cells were investigated with regard to their cell lineage trees using the tTt tracking software, it appeared that the cell cycle length in response to growth factors was reduced in the knockout. Furthermore, when Tnc knockout NPCs were induced to differentiate by the removal of FGF2 and EGF glial differentiation was enhanced. We conclude that the constituent of the stem cell niche Tnc contributes to preserve stemness of NPCs.
    Keywords Extracellular matrix ; Cell lineage ; Gliogenesis ; Growth factor responsiveness ; Stem cell niche ; Tenascin-C ; Time-lapse video microscopy ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher The Company of Biologists
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Asymmetric division events promote variability in cell cycle duration in animal cells and Escherichia coli

    Ulrich Berge / Daria Bochenek / Ralf Schnabel / Arne Wehling / Timm Schroeder / Tanja Stadler / Ruth Kroschewski

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter ... ...

    Abstract We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter cell cycle duration are driven by asymmetric divisions.
    Keywords Science ; Q
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Asymmetric division events promote variability in cell cycle duration in animal cells and Escherichia coli

    Ulrich Berge / Daria Bochenek / Ralf Schnabel / Arne Wehling / Timm Schroeder / Tanja Stadler / Ruth Kroschewski

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter ... ...

    Abstract We know that variations in cell cycle duration between cells naturally occur but the mechanisms are largely unknown. Here, using lineage tracking, hierarchical clustering and Monte Carlo methods, the authors show that large differences in granddaughter cell cycle duration are driven by asymmetric divisions.
    Keywords Science ; Q
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Open-source personal pipetting robots with live-cell incubation and microscopy compatibility

    Philip Dettinger / Tobias Kull / Geethika Arekatla / Nouraiz Ahmed / Yang Zhang / Florin Schneiter / Arne Wehling / Daniel Schirmacher / Shunsuke Kawamura / Dirk Loeffler / Timm Schroeder

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Liquid handling and pipetting tools can automate repetitive tasks but are far from universally used. Here the authors report the Pipetting Helper Imaging Lid (PHIL), an open-source liquid handling robot designed for inexperienced users, that they use for ...

    Abstract Liquid handling and pipetting tools can automate repetitive tasks but are far from universally used. Here the authors report the Pipetting Helper Imaging Lid (PHIL), an open-source liquid handling robot designed for inexperienced users, that they use for automated pipetting.
    Keywords Science ; Q
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Aneley Montaner / Themis Taynah da Silva Santana / Timm Schroeder / Marcelo Einicker-Lamas / Javier Girardini / Marcos Romualdo Costa / Claudia Banchio

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

    2019  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates

    Harunobu Kagawa / Ren Shimamoto / Shin-Il Kim / Fabian Oceguera-Yanez / Takuya Yamamoto / Timm Schroeder / Knut Woltjen

    Stem Cell Reports, Vol 12, Iss 2, Pp 319-

    2019  Volume 332

    Abstract: Summary: During somatic cell reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts undergo dynamic molecular changes, including a mesenchymal-to-epithelial transition (MET) and gain of pluripotency; processes that are influenced by ... ...

    Abstract Summary: During somatic cell reprogramming to induced pluripotent stem cells (iPSCs), fibroblasts undergo dynamic molecular changes, including a mesenchymal-to-epithelial transition (MET) and gain of pluripotency; processes that are influenced by Yamanaka factor stoichiometry. For example, in early reprogramming, high KLF4 levels are correlated with the induction of functionally undefined, transiently expressed MET genes. Here, we identified the cell-surface protein TROP2 as a marker for cells with transient MET induction in the high-KLF4 condition. We observed the emergence of cells expressing the pluripotency marker SSEA-1+ mainly from within the TROP2+ fraction. Using TROP2 as a marker in CRISPR/Cas9-mediated candidate screening of MET genes, we identified the transcription factor OVOL1 as a potential regulator of an alternative epithelial cell fate characterized by the expression of non-iPSC MET genes and low cell proliferation. Our study sheds light on how reprogramming factor stoichiometry alters the spectrum of intermediate cell fates, ultimately influencing reprogramming outcomes. : Woltjen and colleagues identified the transcription factor OVOL1 as a potential regulator of transient MET induction in high-KLF4 reprogramming. Transient MET induction inhibits the expansion of intermediate partially reprogrammed cells. Their study provides insight into how reprogramming factor stoichiometry affects intermediate cell fates and reprogramming outcomes. Keywords: iPSC, reprogramming, stoichiometry, Klf4, mesenchymal-to-epithelial transition, Tacstd2, TROP2, Ovol1, SSEA-1, CRISPR/Cas9
    Keywords Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Lineage marker synchrony in hematopoietic genealogies refutes the PU.1/GATA1 toggle switch paradigm

    Michael K. Strasser / Philipp S. Hoppe / Dirk Loeffler / Konstantinos D. Kokkaliaris / Timm Schroeder / Fabian J. Theis / Carsten Marr

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 10

    Abstract: The timing of cell fate choices is usually unknown, because we have to rely on indirect evidence of their molecular basis. Here, the authors introduce a method to infer decision times from marker onset in cell genealogies, and find evidence refuting the ... ...

    Abstract The timing of cell fate choices is usually unknown, because we have to rely on indirect evidence of their molecular basis. Here, the authors introduce a method to infer decision times from marker onset in cell genealogies, and find evidence refuting the paradigmatic PU.1/GATA1 cell fate switch.
    Keywords Science ; Q
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Nano-scale microfluidics to study 3D chemotaxis at the single cell level.

    Corina Frick / Philip Dettinger / Jörg Renkawitz / Annaïse Jauch / Christoph T Berger / Mike Recher / Timm Schroeder / Matthias Mehling

    PLoS ONE, Vol 13, Iss 6, p e

    2018  Volume 0198330

    Abstract: Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on ... ...

    Abstract Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controllability of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial Identities in Post-Mitotic Cells

    Aneley Montaner / Themis Taynah da Silva Santana / Timm Schroeder / Marcelo Einiker-Lamas / Javier Girardini / Marcos Romualdo Costa / Claudia Banchio

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: Abstract Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the ...

    Abstract Abstract Hitherto, the known mechanisms underpinning cell-fate specification act on neural progenitors, affecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation at the expense of astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial differentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell differentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specification and further support the notion that cell differentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specification in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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