Niebert, Marcus

[["dc.bibliographiccitation.artnumber","385"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Dannenberg, Julia"],["dc.contributor.author","Arnoldt, Mauricio"],["dc.contributor.author","Niebert, Marcus"],["dc.date.accessioned","2018-11-07T10:08:36Z"],["dc.date.available","2018-11-07T10:08:36Z"],["dc.date.issued","2016"],["dc.description.abstract","Mutations in methyl-CpG-binding protein 2 (MECP2) gene have been shown to manifest in a neurodevelopmental disorder that is called Rett syndrome. A typical problem that occurs during development is a disturbance of breathing. To address the role of inhibitory neurons, we generated a mouse line that restores MECP2 in inhibitory neurons in the brainstem by crossbreeding a mouse line that expresses the Cre-recombinase (Cre) in inhibitory neurons under the control of the glycine transporter 2 (GIyT2, slc6a5) promotor(GlyT2-Cre) with a mouse line that has a floxed-stop mutation of the Mecp2 gene (Mecp2(stop/y)). Unrestrained whole-body-plethysmography at postnatal day P60 revealed a low respiratory rate and prolonged respiratory pauses in Mecp2(stop/y) mice. In contrast, G/yT2-Cre positive Mecp2(stop/y) mice (Cre; Mecp2(stop/y)) showed greatly improved respiration and were indistinguishable from wild type littermates. These data support the concept that alterations in inhibitory neurons are important for the development of the respiratory phenotype in Rett syndrome."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.3389/fphys.2016.00385"],["dc.identifier.isi","000382923200001"],["dc.identifier.pmid","27672368"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39494"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.eissn","1664-042X"],["dc.relation.issn","1664-042X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","GlyT2-Dependent Preservation of MECP2-Expression in Inhibitory Neurons Improves Early Respiratory Symptoms but Does Not Rescue Survival in a Mouse Model of Rett Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","15"],["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Balakrishnan, Saju"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:18:21Z"],["dc.date.available","2018-11-07T10:18:21Z"],["dc.date.issued","2016"],["dc.description.abstract","Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2(-/y) mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2(-/y) mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2(-/y) mice. This weaker potentiation in Mecp2(-/y) mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (l(h)) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP-dependent plasticity was also impaired in the Mecp2(-/y) mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2(-/y) mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LIP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect."],["dc.identifier.doi","10.3389/fncel.2016.00015"],["dc.identifier.isi","000369141400003"],["dc.identifier.pmid","26869885"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12888"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41420"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1662-5102"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2(-/y)) Mice by Rolipram"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1821"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Biomaterials"],["dc.bibliographiccitation.lastpage","1829"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Ladewig, Katharina"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Xu, Zhi Ping"],["dc.contributor.author","Gray, Peter P."],["dc.contributor.author","Lu, G. Q."],["dc.date.accessioned","2018-11-07T08:45:12Z"],["dc.date.available","2018-11-07T08:45:12Z"],["dc.date.issued","2010"],["dc.description.abstract","Although siRNAs have surpassed expectations in experiments to alter gene expression in vitro, the lack of an efficient in vivo delivery system still remains a challenge in siRNA therapeutics development and has been recognized as a major hurdle for clinical applications. in this paper we describe an inorganic nanoparticle-based delivery system that is readily adaptable for in vivo systems. Layered double hydroxide (LDH) nanoparticles, a family of inorganic crystals, tightly bind, protect, and release siRNA molecules and deliver them efficiently to mammalian cells in vitro. The uptake of siRNA-loaded LDH nanoparticles occurs via endocytosis, whereby the nanoparticles dissolve due to the low pH in the endosome, thereby aiding endosomal escape into the cytoplasm. The influence of LDH nanoparticles on cell viability and proliferation is negligible at concentrations <= 0.050 mg mL(-1), and a pronounced down-regulation of protein expression upon LDH mediated siRNA transfection of HEK293T cells is observed. (C) 2009 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.biomaterials.2009.10.058"],["dc.identifier.isi","000274354400040"],["dc.identifier.pmid","19922997"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20382"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Sci Ltd"],["dc.relation.issn","0142-9612"],["dc.title","Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4118"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","4128"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Manzke, Till"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Koch, Uwe R."],["dc.contributor.author","Caley, Alex"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Ponimaskin, Evgeni G."],["dc.contributor.author","Mueller, Ulrike"],["dc.contributor.author","Smart, Trevor G."],["dc.contributor.author","Harvey, Robert J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:37:37Z"],["dc.date.available","2018-11-07T08:37:37Z"],["dc.date.issued","2010"],["dc.description.abstract","Rhythmic breathing movements originate from a dispersed neuronal network in the medulla and pons. Here, we demonstrate that rhythmic activity of this respiratory network is affected by the phosphorylation status of the inhibitory glycine receptor alpha 3 subtype (GlyR alpha 3), which controls glutamatergic and glycinergic neuronal discharges, subject to serotonergic modulation. Serotonin receptor type 1A-specific (5-HTR(1A)-specific) modulation directly induced dephosphorylation of GlyR alpha 3 receptors, which augmented inhibitory glycine-activated chloride currents in HEK293 cells coexpressing 5-HTR(1A) and GlyR alpha 3. The 5-HTR(1A)-GlyR alpha 3 signaling pathway was distinct from opioid receptor signaling and efficiently counteracted opioid-induced depression of breathing and consequential apnea in mice. Paradoxically, this rescue of breathing originated from enhanced glycinergic synaptic inhibition of glutamatergic and glycinergic neurons and caused disinhibition of their target neurons. Together, these effects changed respiratory phase alternations and ensured rhythmic breathing in vivo. GlyR alpha 3-deficient mice had an irregular respiratory rhythm under baseline conditions, and systemic 5-HTR(1A) activation failed to remedy opioid-induced respiratory depression in these mice. Delineation of this 5-HTR(1A)-GlyR alpha 3 signaling pathway offers a mechanistic basis for pharmacological treatment of opioid-induced apnea and other breathing disturbances caused by disorders of inhibitory synaptic transmission, such as hyperekplexia, hypoxia/ischemia, and brainstem infarction."],["dc.identifier.doi","10.1172/JCI43029"],["dc.identifier.isi","000283621800043"],["dc.identifier.pmid","20978350"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18577"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Clinical Investigation Inc"],["dc.relation.issn","0021-9738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Serotonin receptor 1A-modulated phosphorylation of glycine receptor alpha 3 controls breathing in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","280"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Applied Clay Science"],["dc.bibliographiccitation.lastpage","289"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Ladewig, Katharina"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Xu, Zhi Ping"],["dc.contributor.author","Gray, Peter P."],["dc.contributor.author","Lu, G. Q."],["dc.date.accessioned","2018-11-07T08:45:09Z"],["dc.date.available","2018-11-07T08:45:09Z"],["dc.date.issued","2010"],["dc.description.abstract","Layered double hydroxides (LDHs) have been known for many decades as catalyst and ceramic precursors, traps for anionic pollutants, catalysts, and additives for polymers, but they recently attracted attention as potential nano-sized carriers for therapeutic/bio-active molecules and genes. Among the many different nanoparticles that have been shown to facilitate gene and/or drug delivery, LDH nanoparticles are particularly well suited for this purpose due to their many desirable properties. In this research Mg(2)Al(OH)(6)NO(3) LDH nanoparticles of varying lateral sizes were synthesized by altering the synthesis conditions. The synthesis conditions particularly influencing the particle size distribution of the LDH suspensions are (a) the temperature during the co-precipitation step and (b) the duration and the temperature of the hydrothermal treatment The association of these nanoparticles with plasmid DNA was studied and it was established that-in contrast to previously published reports-for the plasmid sizes used no significant intercalation occurs. The plasmids wrap around individual particles instead and aggregation of particles is observed. However, due to the observed strong interaction between LDH nanoparticles and DNA, the particles were nonetheless evaluated as transfection agents for mammalian cells. Considerable transfection efficiencies when transfecting adherent cell lines (i.e., HEK293T, NIH 3T3, COS-7, and CHO-K1) were observed, while the transfection of suspension CHO-S cells remained unsuccessful. This is attributed to the formation of aggregates upon DNA-LDH complex formation which settle on top of adherent cells but due to the constant agitation of suspension cultures not on the surface of e.g., CHO-S cells. (C) 2009 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.clay.2009.11.032"],["dc.identifier.isi","000276010700041"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0169-1317"],["dc.title","Controlled preparation of layered double hydroxide nanoparticles and their application as gene delivery vehicles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","173"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","191"],["dc.bibliographiccitation.volume","597"],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Oke, Yoshihiko"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Latal, A. Tobias"],["dc.contributor.author","Fortuna, Michal G."],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Fischer, Julia"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.date.accessioned","2019-07-30T07:09:26Z"],["dc.date.available","2019-07-30T07:09:26Z"],["dc.date.issued","2019"],["dc.description.abstract","Newborn mice produce ultrasonic vocalization to communicate with their mother. The neuronal glycine transporter (GlyT2) is required for efficient loading of synaptic vesicles in glycinergic neurons. Mice lacking GlyT2 develop a phenotype that resembles human hyperekplexia and the mice die in the second postnatal week. In the present study, we show that GlyT2-knockout mice do not acquire adult ultrasonic vocalization-associated breathing patterns. Despite the strong impairment of glycinergic inhibition, they can produce sufficient expiratory airflow to produce ultrasonic vocalization. Because mouse ultrasonic vocalization is a valuable read-out in translational research, these data are highly relevant for a broad range of research fields."],["dc.identifier.doi","10.1113/JP276976"],["dc.identifier.pmid","30296333"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/62159"],["dc.language.iso","en"],["dc.relation.eissn","1469-7793"],["dc.relation.issn","0022-3751"],["dc.relation.issn","1469-7793"],["dc.title","The postnatal development of ultrasonic vocalization-associated breathing is altered in glycine transporter 2-deficient mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","28"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Bischoff, Anne M."],["dc.contributor.author","Hülsmann, Swen"],["dc.contributor.author","Manzke, Till"],["dc.date.accessioned","2019-07-09T11:45:09Z"],["dc.date.available","2019-07-09T11:45:09Z"],["dc.date.issued","2018"],["dc.description.abstract","Mutations in the transcription factor methyl-CpG-binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). Besides many other neurological problems, RTT patients show irregular breathing with recurrent apneas or breath-holdings. MeCP2-deficient mice, which recapitulate this breathing phenotype, show a dysregulated, persistent expression of G-protein-coupled serotonin receptor 5-ht5b (Htr5b) in the brainstem. To investigate whether the persistence of 5-ht5b expression is contributing to the respiratory phenotype, we crossbred MeCP2-deficient mice with 5-ht5b-deficient mice to generate double knockout mice (Mecp2-/y ;Htr5b-/-). To compare respiration between wild type (WT), Mecp2-/y and Mecp2-/y ;Htr5b-/- mice, we used unrestrained whole-body plethysmography. While the breathing of MeCP2-deficient male mice (Mecp2-/y ) at postnatal day 40 is characterized by a slow breathing rate and the occurrence of prolonged respiratory pauses, we found that in MeCP2-deficient mice, which also lacked the 5-ht5b receptor, the breathing rate and the number of pauses were indistinguishable from WT mice. To test for a potential mechanism, we also analyzed if the known coupling of 5-ht5b receptors to Gi proteins is altering second messenger signaling. Tissue cAMP levels in the medulla of Mecp2-/y mice were decreased as compared to WT mice. In contrast, cAMP levels in Mecp2-/y ;Htr5b-/- mice were indistinguishable from WT mice. Taken together, our data points towards a role of 5-ht5b receptors within the complex breathing phenotype of MeCP2-deficient mice."],["dc.identifier.doi","10.3389/fnmol.2018.00028"],["dc.identifier.pmid","29515365"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15043"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59167"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Persistent Expression of Serotonin Receptor 5b Alters Breathing Behavior in Male MeCP2 Knockout Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","43"],["dc.bibliographiccitation.journal","Respiratory Physiology & Neurobiology"],["dc.bibliographiccitation.lastpage","47"],["dc.bibliographiccitation.volume","248"],["dc.contributor.author","Mesuret, Guillaume"],["dc.contributor.author","Dannenberg, Julia"],["dc.contributor.author","Arnoldt, Mauricio"],["dc.contributor.author","Grützner, Anja-Annett"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Hülsmann, Swen"],["dc.date.accessioned","2020-12-10T15:21:04Z"],["dc.date.available","2020-12-10T15:21:04Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.resp.2017.11.011"],["dc.identifier.issn","1569-9048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72907"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Breathing disturbances in a model of Rett syndrome: A potential involvement of the glycine receptor α3 subunit?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","23419"],["dc.bibliographiccitation.issue","26"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","23431"],["dc.bibliographiccitation.volume","286"],["dc.contributor.author","Salonikidis, Petrus S."],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Ullrich, Tim"],["dc.contributor.author","Bao, Guobin"],["dc.contributor.author","Zeug, Andre"],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:54:48Z"],["dc.date.available","2018-11-07T08:54:48Z"],["dc.date.issued","2011"],["dc.description.abstract","Ratiometric measurements with FRET-based biosensors in living cells using a single fluorescence excitation wavelength are often affected by a significant ion sensitivity and the aggregation behavior of the FRET pair. This is an important problem for quantitative approaches. Here we report on the influence of physiological ion concentration changes on quantitative ratiometric measurements by comparing different FRET pairs for a cAMP-detecting biosensor. We exchanged the enhanced CFP/enhanced YFP FRET pair of an established Epac1-based biosensor by the fluorophores mCerulean/mCitrine. In the case of enhanced CFP/enhanced YFP, we showed that changes in proton, and (to a lesser extent) chloride ion concentrations result in incorrect ratiometric FRET signals, which may exceed the dynamic range of the biosensor. Calcium ions have no direct, but an indirect pH-driven effect by mobilizing protons. These ion dependences were greatly eliminated when mCerulean/mCitrine fluorophores were used. For such advanced FRET pairs the biosensor is less sensitive to changes in ion concentration and allows consistent cAMP concentration measurements under different physiological conditions, as occur in metabolically active cells. In addition, we verified that the described FRET pair exchange increased the dynamic range of the FRET efficiency response. The time window for stable experimental conditions was also prolonged by a faster biosensor expression rate in transfected cells and a greatly reduced tendency to aggregate, which reduces cytotoxicity. These properties were verified in functional tests in single cells co-expressing the biosensor and the 5-HT1A receptor."],["dc.identifier.doi","10.1074/jbc.M111.236869"],["dc.identifier.isi","000292025000073"],["dc.identifier.pmid","21454618"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7623"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22755"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","An Ion-insensitive cAMP Biosensor for Long Term Quantitative Ratiometric Fluorescence Resonance Energy Transfer (FRET) Measurements under Variable Physiological Conditions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e32287"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Rolf, Hans J."],["dc.contributor.author","Niebert, Sabine"],["dc.contributor.author","Niebert, Marcus"],["dc.contributor.author","Gaus, Lena"],["dc.contributor.author","Schliephake, Henning"],["dc.contributor.author","Wiese, K. Guenter"],["dc.date.accessioned","2018-11-07T09:13:24Z"],["dc.date.available","2018-11-07T09:13:24Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: The octamer-binding transcription factor 4 (Oct4) was originally described as a marker of embryonic stem cells. Recently, the role of Oct4 as a key regulator in pluripotency was shown by its ability to reprogram somatic cells in vitro, either alone or in concert with other factors. While artificial induction of pluripotency using transcription factors is possible in mammalian cell culture, it remains unknown whether a potential natural transfer mechanism might be of functional relevance in vivo. The stem cell based regeneration of deer antlers is a unique model for rapid and complete tissue regeneration in mammals and therefore most suitable to study such mechanisms. Here, the transfer of pluripotency factors from resident stem cell niche cells to differentiated cells could recruit more stem cells and start rapid tissue regeneration. Methodology/Principal Findings: We report on the ability of STRO-1(+) deer antlerogenic mesenchymal stem cells (DaMSCs) to transport Oct4 via direct cell-to-cell connections. Upon cultivation in stem cell expansion medium, we observed nuclear Oct4 expression in nearly all cells. A number of these cells exhibit Oct4 expression not only in the nucleus, but also with perinuclear localisation and within far-ranging intercellular connections. Furthermore, many cells showed intercellular connections containing both F-actin and alpha-tubulin and through which transport could be observed. To proof that intercellular Oct4-transfer has functional consequences in recipient cells we used a co-culture approach with STRO-1(+) DaMSCs and a murine embryonic fibroblast indicator cell line (Oct4-GFP MEF). In this cell line a reporter gene (GFP) under the control of an Oct4 responsive element is only expressed in the presence of Oct4. GFP expression in Oct4-GFP cells started after 24 hours of co-culture providing evidence of Oct4 transfer from STRO-1(+) DaMSCs to Oct4-GFP MEF target cells. Conclusions: Our findings indicate a possible mechanism for the expansion of a resident stem cell niche by induction of pluripotency in surrounding non-niche cells via transfer of transcription factors through intercellular connections. This provides a new approach to explain the rapid annual antler regrowth."],["dc.identifier.doi","10.1371/journal.pone.0032287"],["dc.identifier.isi","000302796200147"],["dc.identifier.pmid","22359678"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7783"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27167"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Intercellular Transport of Oct4 in Mammalian Cells: A Basic Principle to Expand a Stem Cell Niche?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]