Patterns of Gene Expression Associated with Pten Deficiency in the Developing Inner Ear
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{"title"=>"Patterns of gene expression associated with Pten deficiency in the developing inner ear", "type"=>"journal", "authors"=>[{"first_name"=>"Hyung Jin", "last_name"=>"Kim", "scopus_author_id"=>"56999452800"}, {"first_name"=>"Jihee", "last_name"=>"Ryu", "scopus_author_id"=>"55584200800"}, {"first_name"=>"Hae Mi", "last_name"=>"Woo", "scopus_author_id"=>"54404153100"}, {"first_name"=>"Samuel Sunghwan", "last_name"=>"Cho", "scopus_author_id"=>"56205779400"}, {"first_name"=>"Min Kyung", "last_name"=>"Sung", "scopus_author_id"=>"56047551500"}, {"first_name"=>"Sang Cheol", "last_name"=>"Kim", "scopus_author_id"=>"55989489800"}, {"first_name"=>"Mi Hyun", "last_name"=>"Park", "scopus_author_id"=>"17135830200"}, {"first_name"=>"Taesung", "last_name"=>"Park", "scopus_author_id"=>"34668299500"}, {"first_name"=>"Soo Kyung", "last_name"=>"Koo", "scopus_author_id"=>"7102367881"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373323930", "sgr"=>"84902515202", "issn"=>"19326203", "pmid"=>"24893171", "scopus"=>"2-s2.0-84902515202", "doi"=>"10.1371/journal.pone.0097544"}, "id"=>"572ace21-a56c-36a9-9da5-9860562e0d5c", "abstract"=>"In inner ear development, phosphatase and tensin homolog (PTEN) is necessary for neuronal maintenance, such as neuronal survival and accurate nerve innervations of hair cells. We previously reported that Pten conditional knockout (cKO) mice exhibited disorganized fasciculus with neuronal apoptosis in spiral ganglion neurons (SGNs). To better understand the genes and signaling networks related to auditory neuron maintenance, we compared the profiles of differentially expressed genes (DEGs) using microarray analysis of the inner ear in E14.5 Pten cKO and wild-type mice. We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%. Among the DEGs, expression levels of candidate genes and expression domains were validated by quantitative real-time RT-PCR and in situ hybridization, respectively. Ingenuity pathway analysis using DEGs identified significant signaling networks associated with apoptosis, cellular movement, and axon guidance (i.e., secreted phosphoprotein 1 (Spp1)-mediated cellular movement and regulator of G-protein signaling 4 (Rgs4)-mediated axon guidance). This result was consistent with the phenotypic defects of SGNs in Pten cKO mice (e.g., neuronal apoptosis, abnormal migration, and irregular nerve fiber patterns of SGNs). From this study, we suggest two key regulatory signaling networks mediated by Spp1 and Rgs4, which may play potential roles in neuronal differentiation of developing auditory neurons.", "link"=>"http://www.mendeley.com/research/patterns-gene-expression-associated-pten-deficiency-developing-inner-ear", "reader_count"=>8, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1519106"], "description"=>"<p>Expression levels of <i>Spp1</i> (A, B) and <i>Rgs4</i> (C, D) were examined by <i>in situ</i> hybridization at E14.5. Both <i>Spp1</i> and <i>Rgs4</i> expression were observed in SGNs. Consistent with the microarray results, expression levels of <i>Spp1</i> and <i>Rgs4</i> were increased in the <i>Pten</i> cKO compared to wild-type mice. Scale bars: 100 µm.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks", "patterns"], "article_id"=>1044533, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097544.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_patterns_of_Spp1_and_Rgs4_during_inner_ear_development_/1044533", "title"=>"Expression patterns of <i>Spp1</i> and <i>Rgs4</i> during inner ear development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-03 03:17:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1519105"], "description"=>"<p>Heat maps for relative gene expression of interest (FDR = 0) obtained from three microarrays comparing <i>Pten</i> cKO to wild-type embryos. Green and red indicate decreased and increased expression, respectively, in <i>Pten</i> cKO mice.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks", "identifies"], "article_id"=>1044532, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097544.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microarray_analysis_identifies_novel_Pten_targets_/1044532", "title"=>"Microarray analysis identifies novel <i>Pten</i> targets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-03 03:17:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1519110", "https://ndownloader.figshare.com/files/1519111"], "description"=>"<div><p>In inner ear development, phosphatase and tensin homolog (PTEN) is necessary for neuronal maintenance, such as neuronal survival and accurate nerve innervations of hair cells. We previously reported that <i>Pten</i> conditional knockout (cKO) mice exhibited disorganized fasciculus with neuronal apoptosis in spiral ganglion neurons (SGNs). To better understand the genes and signaling networks related to auditory neuron maintenance, we compared the profiles of differentially expressed genes (DEGs) using microarray analysis of the inner ear in E14.5 <i>Pten</i> cKO and wild-type mice. We identified 46 statistically significant transcripts using significance analysis of microarrays, with the false-discovery rate set at 0%. Among the DEGs, expression levels of candidate genes and expression domains were validated by quantitative real-time RT-PCR and <i>in situ</i> hybridization, respectively. Ingenuity pathway analysis using DEGs identified significant signaling networks associated with apoptosis, cellular movement, and axon guidance (i.e., secreted phosphoprotein 1 (<i>Spp1</i>)-mediated cellular movement and regulator of G-protein signaling 4 (<i>Rgs4</i>)-mediated axon guidance). This result was consistent with the phenotypic defects of SGNs in <i>Pten</i> cKO mice (e.g., neuronal apoptosis, abnormal migration, and irregular nerve fiber patterns of SGNs). From this study, we suggest two key regulatory signaling networks mediated by <i>Spp1</i> and <i>Rgs4</i>, which may play potential roles in neuronal differentiation of developing auditory neurons.</p></div>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks", "patterns", "deficiency"], "article_id"=>1044537, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0097544.s001", "https://dx.doi.org/10.1371/journal.pone.0097544.s002"], "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Patterns_of_Gene_Expression_Associated_with_Pten_Deficiency_in_the_Developing_Inner_Ear/1044537", "title"=>"Patterns of Gene Expression Associated with <i>Pten</i> Deficiency in the Developing Inner Ear", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-06-03 03:17:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1519108"], "description"=>"<p>Genes selected for validation of microarray data by qRT-PCR.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks", "validation", "microarray"], "article_id"=>1044535, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097544.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_selected_for_validation_of_microarray_data_by_qRT_PCR_/1044535", "title"=>"Genes selected for validation of microarray data by qRT-PCR.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-03 03:17:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1519109"], "description"=>"<p>Differentially expressed genes in wild-type and <i>Pten</i> cKO mice at E14.5.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks", "genes", "wild-type", "cko", "mice"], "article_id"=>1044536, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097544.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differentially_expressed_genes_in_wild_type_and_Pten_cKO_mice_at_E14_5_/1044536", "title"=>"Differentially expressed genes in wild-type and <i>Pten</i> cKO mice at E14.5.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-03 03:17:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1519107"], "description"=>"<p>Network analysis using the Ingenuity Pathway Analysis (IPA) software was conducted using selected genes that were differentially expressed and their close relationships. IPA results show two core networks consisted of <i>Spp1</i>-(red line) and <i>Rgs4</i>-associated interactions (blue line). Genes that were differentially expressed are indicated in pink, and predicted interacting genes (not contained in the microarray data) are indicated in white. Axon guidance signaling pathway-related genes are outlined in magenta. Molecular interactions between connected genes represent direct (solid line) or indirect (dotted line) functional relationships based on the IPA database. Green indicates negative fold changes, while red denotes positive fold changes, according to color intensity.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Developmental signaling", "Molecular cell biology", "developmental biology", "Cell differentiation", "embryology", "genetics", "gene expression", "neuroscience", "Cellular neuroscience", "Axon guidance", "neurogenesis", "Sensory systems", "Auditory system", "Developmental neuroscience", "Molecular neuroscience", "neural networks"], "article_id"=>1044534, "categories"=>["Biological Sciences"], "users"=>["Hyung Jin Kim", "Jihee Ryu", "Hae-Mi Woo", "Samuel Sunghwan Cho", "Min Kyung Sung", "Sang Cheol Kim", "Mi-Hyun Park", "Taesung Park", "Soo Kyung Koo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0097544.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_network_analysis_associated_with_Pten_deficient_inner_ear_/1044534", "title"=>"Functional network analysis associated with <i>Pten</i>-deficient inner ear.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-03 03:17:22"}

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