The L-type Ca2+ Channels Blocker Nifedipine Represses Mesodermal Fate Determination in Murine Embryonic Stem Cells
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{"title"=>"The L-type Ca2+ Channels Blocker Nifedipine Represses Mesodermal Fate Determination in Murine Embryonic Stem Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Filomain", "last_name"=>"Nguemo", "scopus_author_id"=>"8922039800"}, {"first_name"=>"Bernd K.", "last_name"=>"Fleischmann", "scopus_author_id"=>"56043655400"}, {"first_name"=>"Manoj K.", "last_name"=>"Gupta", "scopus_author_id"=>"56575803900"}, {"first_name"=>"Tomo", "last_name"=>"Šarić", "scopus_author_id"=>"6603401782"}, {"first_name"=>"Daniela", "last_name"=>"Malan", "scopus_author_id"=>"7005099209"}, {"first_name"=>"Huamin", "last_name"=>"Liang", "scopus_author_id"=>"22954139500"}, {"first_name"=>"Kurt", "last_name"=>"Pfannkuche", "scopus_author_id"=>"6504449086"}, {"first_name"=>"Wilhelm", "last_name"=>"Bloch", "scopus_author_id"=>"35481516500"}, {"first_name"=>"Heribert", "last_name"=>"Schunkert", "scopus_author_id"=>"7006507139"}, {"first_name"=>"Jürgen", "last_name"=>"Hescheler", "scopus_author_id"=>"56213247900"}, {"first_name"=>"Michael", "last_name"=>"Reppel", "scopus_author_id"=>"6603474927"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23320083", "doi"=>"10.1371/journal.pone.0053407", "pui"=>"368093949", "issn"=>"19326203", "sgr"=>"84872192952", "scopus"=>"2-s2.0-84872192952"}, "id"=>"c5e75133-ed9b-34c7-af40-299f26ddac67", "abstract"=>"Dihydropyridines (DHP), which nifedipine is a member of, preferentially block Ca(2+) channels of different cell types. Moreover, influx of Ca(2+) through L-type Ca(2+) channels (LTCCs) activates Ca(2+) signaling pathways, which in turn contribute to numerous cellular processes. Although LTCCs are expressed in undifferentiated cells, very little is known about its contributions to the transcriptional regulation of mesodermal and cardiac genes. This study aimed to examine the contribution of LTCCs and the effect of nifedipine on the commitment of pluripotent stem cells toward the cardiac lineage in vitro. The murine embryonic stem (ES, cell line D3) and induced pluripotent stem (iPS, cell clone 09) cells were differentiated into enhanced green fluorescence protein (EGFP) expressing spontaneously beating cardiomyocytes (CMs). Early treatment of differentiating cells with 10 µM nifedipine led to a significant inhibition of the cardiac mesoderm formation and cardiac lineage commitment as revealed by gene regulation analysis. This was accompanied by the inhibition of spontaneously occurring Ca(2+) transient and reduction of LTCCs current density (I(CaL)) of differentiated CMs. In addition, nifedipine treatment instigated a pronounced delay of the spontaneous beating embryoid body (EB) and led to a poor surface localization of L-type Ca(2+) channel α(1C) (Ca(V)1.2) subunits. Contrary late incubation of pluripotent stem cells with nifedipine was without any impact on the differentiation process and did not affect the derived CMs function. Our data indicate that nifedipine blocks the determined path of pluripotent stem cells to cardiomyogenesis by inhibition of mesodermal commitment at early stages of differentiation, thus the proper upkeep Ca(2+) concentration and pathways are essentially required for cardiac gene expression, differentiation and function.", "link"=>"http://www.mendeley.com/research/ltype-ca2-channels-blocker-nifedipine-represses-mesodermal-fate-determination-murine-embryonic-stem", "reader_count"=>27, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>5, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>5, "Neuroscience"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Portugal"=>1, "Spain"=>1, "Russia"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/512406"], "description"=>"<p>(<b><i>A</i></b>) Protocol used to determine the effect of nifedipine application during cell differentiation. Note that for beating EBs and single cell electrophysiology and Ca2+ imaging experiments, analysis was performed at least 24 hours after washout to reflect long-term changes instead of acute drugs effects. (<b><i>B–C</i></b>) Representative experiments showing EBs with GFP expressing areas cultured under control conditions (<i>B</i>) and after nifedipine-treatment (10 µM) (<i>C</i>) of ES cells. (<b><i>D–F</i></b>) Representative EBs showing EGFP+ CMs differentiated of ES cells under control conditions (<b><i>D</i></b>), after nifedipine- (<b><i>E</i></b>) and BayK8644- (<b><i>F</i></b>) treatment. (<b>G</b>) Representative FACS analysis of ES cell-derived CMs generated under control, nifedipine- and BayK8644-treated conditions. (Scale bars 50 µm (B, C) and 20 µm (D–F).</p>", "links"=>[], "tags"=>["nifedipine", "inhibits", "differentiation", "es", "cell-derived"], "article_id"=>182880, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_presence_of_nifedipine_in_culture_medium_inhibits_differentiation_of_ES_cell_derived_CMs_/182880", "title"=>"The presence of nifedipine in culture medium inhibits differentiation of ES cell-derived CMs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 00:48:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/278288", "https://ndownloader.figshare.com/files/278346", "https://ndownloader.figshare.com/files/278376", "https://ndownloader.figshare.com/files/278421", "https://ndownloader.figshare.com/files/278464", "https://ndownloader.figshare.com/files/278495", "https://ndownloader.figshare.com/files/278624", "https://ndownloader.figshare.com/files/278676"], "description"=>"<div><p>Dihydropyridines (DHP), which nifedipine is a member of, preferentially block Ca<sup>2+</sup> channels of different cell types. Moreover, influx of Ca<sup>2+</sup> through L-type Ca<sup>2+</sup> channels (LTCCs) activates Ca<sup>2+</sup> signaling pathways, which in turn contribute to numerous cellular processes. Although LTCCs are expressed in undifferentiated cells, very little is known about its contributions to the transcriptional regulation of mesodermal and cardiac genes. This study aimed to examine the contribution of LTCCs and the effect of nifedipine on the commitment of pluripotent stem cells toward the cardiac lineage <em>in vitro</em>. The murine embryonic stem (ES, cell line D3) and induced pluripotent stem (iPS, cell clone 09) cells were differentiated into enhanced green fluorescence protein (EGFP) expressing spontaneously beating cardiomyocytes (CMs). Early treatment of differentiating cells with 10 µM nifedipine led to a significant inhibition of the cardiac mesoderm formation and cardiac lineage commitment as revealed by gene regulation analysis. This was accompanied by the inhibition of spontaneously occurring Ca<sup>2+</sup> transient and reduction of LTCCs current density (<em>I</em><sub>CaL</sub>) of differentiated CMs. In addition, nifedipine treatment instigated a pronounced delay of the spontaneous beating embryoid body (EB) and led to a poor surface localization of L-type Ca<sup>2+</sup> channel α<sub>1C</sub> (Ca<sub>V</sub>1.2) subunits. Contrary late incubation of pluripotent stem cells with nifedipine was without any impact on the differentiation process and did not affect the derived CMs function. Our data indicate that nifedipine blocks the determined path of pluripotent stem cells to cardiomyogenesis by inhibition of mesodermal commitment at early stages of differentiation, thus the proper upkeep Ca<sup>2+</sup> concentration and pathways are essentially required for cardiac gene expression, differentiation and function.</p> </div>", "links"=>[], "tags"=>["l-type", "channels", "blocker", "nifedipine", "represses", "mesodermal", "murine", "embryonic", "cells"], "article_id"=>114862, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0053407.s001", "https://dx.doi.org/10.1371/journal.pone.0053407.s002", "https://dx.doi.org/10.1371/journal.pone.0053407.s003", "https://dx.doi.org/10.1371/journal.pone.0053407.s004", "https://dx.doi.org/10.1371/journal.pone.0053407.s005", "https://dx.doi.org/10.1371/journal.pone.0053407.s006", "https://dx.doi.org/10.1371/journal.pone.0053407.s007", "https://dx.doi.org/10.1371/journal.pone.0053407.s008"], "stats"=>{"downloads"=>43, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_L_type_Ca_2_Channels_Blocker_Nifedipine_Represses_Mesodermal_Fate_Determination_in_Murine_Embryonic_Stem_Cells__/114862", "title"=>"The L-type Ca<sup>2+</sup> Channels Blocker Nifedipine Represses Mesodermal Fate Determination in Murine Embryonic Stem Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-08 01:21:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/513793"], "description"=>"<p><b>Abbreviations:</b> n, indicates the cell number; APD50/APD90, AP duration measured at 50% or 90% of repolarization; dV/dtmax, maximum rate of rise of AP; and MDP, maximum diastolic potential.</p>*<p>P<0.05 compared with control condition.</p>", "links"=>[], "tags"=>["parameters", "cms", "ebs", "generated", "nifedipine-treated"], "article_id"=>184273, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_AP_parameters_of_CMs_obtained_from_EBs_generated_under_control_and_nifedipine_treated_conditions_/184273", "title"=>"AP parameters of CMs obtained from EBs generated under control and nifedipine-treated conditions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-08 01:11:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/513699"], "description"=>"<p>(<b><i>A</i></b>) Representative tracings of spontaneous Ca<sup>2+</sup> transients recorded in spontaneously beating CMs from control and nifedipine-treated cultures. Fluorescence images (labeled with Fura 2 AM) of the recorded cells are shown on the left panel. (<b><i>B</i></b>) Left, spontaneous Ca<sup>2+</sup> transients recorded from CMs derived under untreated (top) and nifedipine-treated (bottom) condition before and after caffeine application. Right, caffeine-induced peak amplitude (top, right) of the Ca<sup>2+</sup> signals and Fractional release (bottom, right) calculated as the ratio of peak Ca<sup>2+</sup> concentration under control condition to peak Ca<sup>2+</sup> concentration induced by caffeine. (<b><i>C–F</i></b>) Comparison of the frequency (<i>C</i>), amplitude (<i>D</i>), maximum upstroke (<i>E</i>) and decay (<i>F</i>) velocity of spontaneous Ca<sup>2+</sup> transients on day 12 in controls (<i>n</i> = 10) and nifedipine-treated <i>(n</i> = 8) cultures.</p>", "links"=>[], "tags"=>["reduced", "spontaneous", "transient", "es", "cell-derived"], "article_id"=>184178, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nifedipine_reduced_spontaneous_Ca_2_transient_activity_in_ES_cell_derived_CMs_/184178", "title"=>"Nifedipine reduced spontaneous Ca<sup>2+</sup> transient activity in ES cell-derived CMs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 01:09:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/513318"], "description"=>"<p>(<b><i>A–B</i></b>) Representative traces (A) and currents densities (B) of Na<sup>+</sup> current recorded from a control and nifedipine-treated cells at days 4 (non-beating cell) and 12 (beating CM) of differentiation. (<b><i>C–D</i></b>) Representative traces and current-voltage relationships (<i>I/V</i>) of the peak depolarization-activated outward K<sup>+</sup> current (<i>I</i><sub>peak</sub>). (<b><i>E–F</i></b>) Effect of acute application of Na<sup>+</sup> channel (<i>E</i>) blocker TTX (1 µM) and non-specific K<sup>+</sup> channel (<i>F</i>) blocker TEA (10 mM). The dotted lines indicate the zero current level.</p>", "links"=>[], "tags"=>["characteristics", "depolarization-activated", "outward"], "article_id"=>183796, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g005", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_characteristics_of_Na_channel_and_depolarization_activated_outward_K_currents_/183796", "title"=>"Functional characteristics of Na<sup>+</sup> channel and depolarization-activated outward K<sup>+</sup> currents.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 01:03:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/512859"], "description"=>"<p>(<b><i>A</i></b>) RT-PCR for L-type Ca<sup>2+</sup> channel α-subunit isoforms in undifferentiated ES cells and CMs at day 12 of differentiation, demonstrating (i) presence of L-type Ca<sup>2+</sup> channel mRNA even in undifferentiated ES cells and (ii) an increase in mRNA encoding the CaV1.2 subunit of the channel. (<b><i>B</i></b>) RT-PCR analyses of cardiac-specific and transcription factors <i>α-MHC/Myh6, ANF/Nppa, MLC2v/Myl2, NKx2.5</i> and <i>GATA4</i> in beating cluster at day 12 of both ES and iPS differentiation. (<b><i>C</i></b>) RT-PCR analyses of representative markers, PECAM-1 (mesoderm, endothelial cell), AFP (endoderm, early hepatocyte progenitor), Nestin and NF-H (ectoderm, neural progenitor) and α-SMA (mesoderm) in ES and iPS beating cluster at day 12 of differentiation. (<b><i>D</i></b>) Quantitative real-time PCR analyses of mesoderm and cardiac markers and specific transcript (<i>Brachyury T, Mesp1, NKx2.5, Tbx5, Mest, Myocd, Myh6/α-MHC, Myl2/MLC2v, and Nppa/ANF</i>), as well as cardiac ionic channels (<i>CACNA1c, KCNH2</i> and <i>SCN5A</i>) expression at different stage of ES cell differentiation. GAPDH was used as housekeeping gene and served to normalize the result. Results are reported as the means±SEM (n = 3). *<i>P</i><0.05 vs. control CMs.</p>", "links"=>[], "tags"=>["repressed", "cardiac", "mesoderm"], "article_id"=>183342, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g003", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nifedipine_repressed_the_expression_level_of_most_specific_cardiac_and_mesoderm_genes_/183342", "title"=>"Nifedipine repressed the expression level of most specific cardiac and mesoderm genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 00:55:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/513516"], "description"=>"<p>(<b><i>A–C</i></b>), Representative L-type Ca<sup>2+</sup> current traces recorded as indicated in protocol (<i>A</i>) from CM cultured in control (<i>B</i>) and nifedipine-treated (<i>C</i>) conditions. (<b><i>D</i></b>) Current densities recorded at the maximal peak of the current (10 mV) of cells generated in control and under nifedipine-treatment at days 8 and 12 of differentiation. (<b><i>E–F</i></b>) Current-voltage relationships (<i>E</i>) and activation curves (<i>F</i>) of <i>I</i><sub>CaL</sub> recorded in control (open symbols) and nifedipine-treated (filled symbols) CMs. (<b><i>G</i></b>), Steady-state inactivation curves of control (open symbols) and nifedipine-treated (filled symbols) CMs. (<b><i>H–I</i></b>) shows the time constants of fast τ<sub>f</sub> (<i>H</i>) and slow τ<sub>s</sub> (<i>I</i>) phases of <i>I</i><sub>CaL</sub> inactivation recorded in ES cell-derived CMs from control and nifedipine-treated cultures. (<b><i>J</i></b>) Immunolocalization of L-type calcium Ca<sub>V</sub>1.2 subunit (α<sub>1C</sub>) in undifferentiated ES cells suggests enrichment in the cell periphery and cellular membrane. (<b><i>K–L</i></b>) Immunocytochemistry of L-type calcium Ca<sub>V</sub>1.2 subunit (α<sub>1C</sub>) in CMs generated under both control (<i>K</i>) and nifedipine-treated (<i>L</i>) conditions. Insert are positive control experiments from the same bath of cells performed with mouse anti-α actinin. Hoechst 33342 was used to stain nuclei (blue). (Scale bars: 20 µm). * denote significant differences to control and <b><sup>†</sup></b> significant differences to day 12 of differentiation.</p>", "links"=>[], "tags"=>["nifedipine", "differentiation", "altered", "cardiac", "es", "cell-derived"], "article_id"=>183995, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g006", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_presence_of_nifedipine_in_differentiation_medium_altered_the_cardiac_I_CaL_density_of_ES_cell_derived_CMs_/183995", "title"=>"The presence of nifedipine in differentiation medium altered the cardiac <i>I</i><sub>CaL</sub> density of ES cell-derived CMs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 01:06:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/513100"], "description"=>"<p>(<b><i>A</i></b>) Representative AP recordings from spontaneously beating ES cell-derived CMs revealed differentiation of nifedipine-treated cell into the different cardiac subtypes: nodal-, embryonic atrial- and embryonic ventricular-like CMs, note the presence of unspecified CMs (left panel). Statistic analysis (right panel) of different cardiac subtypes generated under control and nifedipine-treated cultures. (<b><i>B–C</i></b>) Representative AP of untreated (<i>B</i>) and nifedipine-treated (<i>C</i>) ES cells-derived CMs showed a prominent positive chronotropic effect of Iso (1 µM) (middle left) and negative chronotropic response to CCh (1 µM) (middle right) application. These effects could be partially reversed by washout. The dotted lines indicate the zero current level.</p>", "links"=>[], "tags"=>["cardiac", "subtypes", "muscarinic"], "article_id"=>183581, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nifedipine_does_not_affect_the_generation_of_specific_cardiac_subtypes_as_well_as_the_946_adrenergic_and_muscarinic_regulation_pathways_/183581", "title"=>"Nifedipine does not affect the generation of specific cardiac subtypes as well as the β-adrenergic and muscarinic regulation pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 00:59:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/512651"], "description"=>"<p>(<b><i>A</i></b>) Time course of the incidence of ES cell-derived contracting EBs generated in the absence (control) or presence of nifedipine or BayK8644. The mean±SEM of the percentage of EBs with contracting areas during differentiation is depicted. (<b><i>B</i></b>) Percentage of beatings EBs at day 12 of differentiation derived from ES cells following nifedipine and BayK8644 administration at different times. Note that addition of nifedipine before day 4 of differentiation reduced the percentage of EBs containing beating CMs significantly below both control and BayK8644 levels. (<b><i>C</i></b>) Percentage of CMs changes from control condition obtained by FACS analysis after 12 days of cell differentiation under nifedipine and BayK8644. Nifedipine and Bayk8644 were applied on days 0 (D0), 2 (D2) and 4 (D4) of differentiation. (<b><i>D–E</i></b>) Immunofluorescence detection of CMs (green) in EBs after 12 days of differentiation. (<b><i>F–G</i></b>) Immunostaining of representative dispersed cells from beating clusters of EBs derived under control and nifedipine-treated conditions with anti-sarcomeric α-actinin (red) (1∶800). (<b><i>H–I</i></b>) Cardiomyocytes isolated from beating areas of EBs at day 12 of differentiation in both control and nifedipine-treated conditions show sarcomeric striations when stained for α-sarcomeric actinin. Insets show the fluorescence intensity of EGFP (red). Hoechst 33342 was used to stain nuclei (blue or magenta). Scale bars: 20 µm.</p>", "links"=>[], "tags"=>["repressed", "cardiac", "differentiation"], "article_id"=>183134, "categories"=>["Molecular Biology", "Cell Biology", "Developmental Biology"], "users"=>["Filomain Nguemo", "Bernd K. Fleischmann", "Manoj K. Gupta", "Tomo Šarić", "Daniela Malan", "Huamin Liang", "Kurt Pfannkuche", "Wilhelm Bloch", "Heribert Schunkert", "Jürgen Hescheler", "Michael Reppel"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0053407.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nifedipine_repressed_the_cardiac_differentiation_profile_/183134", "title"=>"Nifedipine repressed the cardiac differentiation profile.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-08 00:52:14"}

PMC Usage Stats | Further Information

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Relative Metric

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