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Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation

Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation

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MEISIG, Johannes, Nadine DRESER, Marion KAPITZA, Margit HENRY, Tamara ROTSHTEYN, Jörg RAHNENFÜHRER, Jan G HENGSTLER, Tanja WALDMANN, Marcel LEIST, Nils BLÜTHGEN, 2020. Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation. In: Nucleic Acids Research. Oxford University Press. 48(22), pp. 12577-12592. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkaa1089

@article{Meisig2020-12-16Kinet-52017, title={Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation}, year={2020}, doi={10.1093/nar/gkaa1089}, number={22}, volume={48}, issn={0305-1048}, journal={Nucleic Acids Research}, pages={12577--12592}, author={Meisig, Johannes and Dreser, Nadine and Kapitza, Marion and Henry, Margit and Rotshteyn, Tamara and Rahnenführer, Jörg and Hengstler, Jan G and Waldmann, Tanja and Leist, Marcel and Blüthgen, Nils} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/52017"> <dc:contributor>Rahnenführer, Jörg</dc:contributor> <dc:contributor>Leist, Marcel</dc:contributor> <dc:creator>Rotshteyn, Tamara</dc:creator> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Rotshteyn, Tamara</dc:contributor> <dc:contributor>Waldmann, Tanja</dc:contributor> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:contributor>Meisig, Johannes</dc:contributor> <dc:creator>Kapitza, Marion</dc:creator> <dc:rights>Attribution-NonCommercial 4.0 International</dc:rights> <dcterms:title>Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation</dcterms:title> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dcterms:rights rdf:resource="http://creativecommons.org/licenses/by-nc/4.0/"/> <dc:creator>Hengstler, Jan G</dc:creator> <dc:contributor>Blüthgen, Nils</dc:contributor> <dc:contributor>Kapitza, Marion</dc:contributor> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52017"/> <dcterms:abstract xml:lang="eng">Thousands of transcriptome data sets are available, but approaches for their use in dynamic cell response modelling are few, especially for processes affected simultaneously by two orthogonal influencing variables. We approached this problem for neuroepithelial development of human pluripotent stem cells (differentiation variable), in the presence or absence of valproic acid (signaling variable). Using few basic assumptions (sequential differentiation states of cells; discrete on/off states for individual genes in these states), and time-resolved transcriptome data, a comprehensive model of spontaneous and perturbed gene expression dynamics was developed. The model made reliable predictions (average correlation of 0.85 between predicted and subsequently tested expression values). Even regulations predicted to be non-monotonic were successfully validated by PCR in new sets of experiments. Transient patterns of gene regulation were identified from model predictions. They pointed towards activation of Wnt signaling as a candidate pathway leading to a redirection of differentiation away from neuroepithelial cells towards neural crest. Intervention experiments, using a Wnt/beta-catenin antagonist, led to a phenotypic rescue of this disturbed differentiation. Thus, our broadly applicable model allows the analysis of transcriptome changes in complex time/perturbation matrices.</dcterms:abstract> <dc:creator>Waldmann, Tanja</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52017/1/Meisig_2-1arx1yp5wfbdz9.pdf"/> <dc:creator>Blüthgen, Nils</dc:creator> <dc:language>eng</dc:language> <dc:creator>Meisig, Johannes</dc:creator> <dc:creator>Dreser, Nadine</dc:creator> <dc:creator>Leist, Marcel</dc:creator> <dc:creator>Rahnenführer, Jörg</dc:creator> <dcterms:issued>2020-12-16</dcterms:issued> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/52017/1/Meisig_2-1arx1yp5wfbdz9.pdf"/> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-12-07T08:22:24Z</dc:date> <dc:contributor>Hengstler, Jan G</dc:contributor> <dc:contributor>Henry, Margit</dc:contributor> <dc:creator>Henry, Margit</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2020-12-07T08:22:24Z</dcterms:available> <dc:contributor>Dreser, Nadine</dc:contributor> </rdf:Description> </rdf:RDF>

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