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Raad, Farah S.
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Raad, Farah S.
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Raad, Farah S.
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Raad, F. S.
Raad, Farah
Raad, F.
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2021Journal Article Research Paper [["dc.bibliographiccitation.artnumber","cmdc.202100222"],["dc.bibliographiccitation.firstpage","3300"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","ChemMedChem"],["dc.bibliographiccitation.lastpage","3305"],["dc.bibliographiccitation.volume","16"],["dc.contributor.affiliation","Raad, Farah S.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Khan, Taukeer A.; 2\r\nDZHK (German Center for Cardiovascular Research) – Partner site Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Esser, Tilman U.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Hudson, James E.; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Seth, Bhakti Irene; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Fujita, Buntaro; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Gandamala, Ravi; 3\r\nInstitute of Organic and Biomolecular Chemistry\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.affiliation","Tietze, Lutz F.; 2\r\nDZHK (German Center for Cardiovascular Research) – Partner site Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zimmermann, Wolfram-Hubertus; 1\r\nInstitute of Pharmacology and Toxicology\r\nUniversity Medical Center\r\nGeorg-August-University\r\nGöttingen Germany"],["dc.contributor.author","Raad, Farah S."],["dc.contributor.author","Khan, Taukeer A."],["dc.contributor.author","Esser, Tilman U."],["dc.contributor.author","Hudson, James E."],["dc.contributor.author","Seth, Bhakti Irene"],["dc.contributor.author","Fujita, Buntaro"],["dc.contributor.author","Gandamala, Ravi"],["dc.contributor.author","Tietze, Lutz F."],["dc.contributor.author","Zimmermann, Wolfram H."],["dc.date.accessioned","2021-10-01T09:58:46Z"],["dc.date.available","2021-10-01T09:58:46Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T00:45:29Z"],["dc.description.abstract","Abstract Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small‐molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two‐tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4’‐hydroxychalcone [4’HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self‐organize into contractile engineered human myocardium (EHM). We identified 4’HC, 4‐fluoro‐4’‐methoxychalcone, and 4‐fluoro‐4’‐hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4’HC as an effective replacement for BMP4 in the derivation of contractile EHM‐forming cardiomyocytes."],["dc.description.abstract","Have a little heart: A screen for mesoderm inducing chalcones in human pluripotent stem cell cultures identified 4’‐hydroxychalcone (4’HC) as an effective replacement for bone‐morphogenetic protein 4 (BMP4) in supporting the derivation of engineered heart muscle (EHM)‐formation competent cardiomyocytes. image"],["dc.description.sponsorship","German Center for Cardiovascular Research"],["dc.description.sponsorship","German Federal Ministry for Science and Education"],["dc.description.sponsorship","German Research Foundation http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Fondation Leducq http://dx.doi.org/10.13039/501100001674"],["dc.identifier.doi","10.1002/cmdc.202100222"],["dc.identifier.pmid","34309224"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/90137"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/432"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1860-7187"],["dc.relation.issn","1860-7179"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Chalcone‐Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]Details DOI PMID PMC2016Journal Article [["dc.bibliographiccitation.artnumber","33"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Genetics"],["dc.bibliographiccitation.lastpage","17"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Zeidler, Sebastian"],["dc.contributor.author","Meckbach, Cornelia"],["dc.contributor.author","Tacke, Rebecca"],["dc.contributor.author","Raad, Farah S."],["dc.contributor.author","Roa, Angelica"],["dc.contributor.author","Uchida, Shizuka"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Wingender, Edgar"],["dc.contributor.author","Gültas, Mehmet"],["dc.date.accessioned","2017-09-07T11:54:27Z"],["dc.date.available","2017-09-07T11:54:27Z"],["dc.date.issued","2016"],["dc.description.abstract","Transcription factors (TFs) regulate gene expression in living organisms. In higher organisms, TFs often interact in non-random combinations with each other to control gene transcription. Understanding the interactions is key to decipher mechanisms underlying tissue development. The aim of this study was to analyze co-occurring transcription factor binding sites (TFBSs) in a time series dataset from a new cell-culture model of human heart muscle development in order to identify common as well as specific co-occurring TFBS pairs in the promoter regions of regulated genes which can be essential to enhance cardiac tissue developmental processes. To this end, we separated available RNAseq dataset into five temporally defined groups: (i) mesoderm induction stage; (ii) early cardiac specification stage; (iii) late cardiac specification stage; (iv) early cardiac maturation stage; (v) late cardiac maturation stage, where each of these stages is characterized by unique differentially expressed genes (DEGs). To identify TFBS pairs for each stage, we applied the MatrixCatch algorithm, which is a successful method to deduce experimentally described TFBS pairs in the promoters of the DEGs. Although DEGs in each stage are distinct, our results show that the TFBS pair networks predicted by MatrixCatch for all stages are quite similar. Thus, we extend the results of MatrixCatch utilizing a Markov clustering algorithm (MCL) to perform network analysis. Using our extended approach, we are able to separate the TFBS pair networks in several clusters to highlight stage-specific co-occurences between TFBSs. Our approach has revealed clusters that are either common (NFAT or HMGIY clusters) or specific (SMAD or AP-1 clusters) for the individual stages. Several of these clusters are likely to play an important role during the cardiomyogenesis. Further, we have shown that the related TFs of TFBSs in the clusters indicate potential synergistic or antagonistic interactions to switch between different stages. Additionally, our results suggest that cardiomyogenesis follows the hourglass model which was already proven for Arabidopsis and some vertebrates. This investigation helps us to get a better understanding of how each stage of cardiomyogenesis is affected by different combination of TFs. Such knowledge may help to understand basic principles of stem cell differentiation into cardiomyocytes"],["dc.identifier.doi","10.3389/fgene.2016.00033"],["dc.identifier.gro","3145188"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13173"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2896"],["dc.language.iso","en"],["dc.notes.intern","Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-8021"],["dc.relation.issn","1664-8021"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Computational Detection of Stage-Specific Transcription Factor Clusters during Heart Development"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]Details DOI