Pax6 Inactivation in the Adult Pancreas Reveals Ghrelin as Endocrine Cell Maturation Marker
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{"title"=>"Pax6 inactivation in the adult pancreas reveals ghrelin as endocrine cell maturation marker", "type"=>"journal", "authors"=>[{"first_name"=>"Zeeshan", "last_name"=>"Ahmad", "scopus_author_id"=>"57089809000"}, {"first_name"=>"Maria", "last_name"=>"Rafeeq", "scopus_author_id"=>"57091010900"}, {"first_name"=>"Patrick", "last_name"=>"Collombat", "scopus_author_id"=>"6508029854"}, {"first_name"=>"Ahmed", "last_name"=>"Mansouri", "scopus_author_id"=>"7006652856"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0144597", "sgr"=>"84956666098", "isbn"=>"1932-6203", "pmid"=>"26658466", "issn"=>"19326203", "scopus"=>"2-s2.0-84956666098", "pui"=>"607918105"}, "id"=>"af4ea05c-c310-31e9-9b10-3a0f2baf5df0", "abstract"=>"The transcription factor Pax6 is an important regulator of development and cell differentiation in various organs. Thus, Pax6 was shown to promote neural development in the cerebral cortex and spinal cord, and to control pancreatic endocrine cell genesis. However, the role of Pax6 in distinct endocrine cells of the adult pancreas has not been addressed. We report the conditional inactivation of Pax6 in insulin and glucagon producing cells of the adult mouse pancreas. In the absence of Pax6, beta- and alpha-cells lose their molecular maturation characteristics. Our findings provide strong evidence that Pax6 is responsible for the maturation of beta-, and alpha-cells, but not of delta-, and PP-cells. Moreover, lineage-tracing experiments demonstrate that Pax6-deficient beta- and alpha-cells are shunted towards ghrelin marked cells, sustaining the idea that ghrelin may represent a marker for endocrine cell maturation.", "link"=>"http://www.mendeley.com/research/pax6-inactivation-adult-pancreas-reveals-ghrelin-endocrine-cell-maturation-marker", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>5, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>9, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Neuroscience"=>{"Neuroscience"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2607245"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from mice that were injected with tamoxifen at 2 months of age and analysed at 3 weeks post tamoxifen induction. Ghrelin<sup>+</sup> cells are not detected in the control islets (a). In the ubiquitous <i>Pax6</i> KO islets, ghrelin expression is up regulated and ghrelin<sup>+</sup> cells may or may not express Pdx1 depending on the fact that they originally come from insulin<sup>+</sup> or glucagon<sup>+</sup> cells, respectively (b).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623744, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g023", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ghrelin_expressing_cells_in_the_islets_of_adult_ubiquitous_Pax6_KO_mice_can_be_differentially_identified_/1623744", "title"=>"Ghrelin expressing cells, in the islets of adult-ubiquitous <i>Pax6</i> KO mice, can be differentially identified.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607178"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2 month old mice at 4 days (a-d) or 4 weeks (g-j) after tamoxifen induction. <i>Pax6</i> expression is lost from a majority of insulin<sup>+</sup> cells (c, d). Ablation of <i>Pax6</i> is specific to YFP labeled cells (i, j) as YFP<sup>-</sup> insulin<sup>+</sup> cells continue to express <i>Pax6</i> (arrows i, j). Quantification of <i>Pax6</i><sup>-</sup> insulin<sup>+</sup> (e) and YFP<sup>+</sup> insulin<sup>+</sup> (f) cells in the pancreata of 2 month old mice at 4 days after tamoxifen induction (n = 3). Error bars represent SEM; *p<0.05.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623683, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Beta_cell_specific_ablation_of_Pax6_/1623683", "title"=>"Beta-cell-specific ablation of <i>Pax6</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607184"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2.5 month old mice at 2 weeks after tamoxifen induction (a-h) or 3.5 month old mice at 6 weeks after tamoxifen induction (i, j). Expression of MafA and Glut2 is lost (e, f), expression of Pdx1 is maintained (g), and that of Nkx6.1 is maintained at 2 weeks (h) but sharply reduced at 6 weeks (j) post-tamoxifen induction in the islets of beta-cell-specific <i>Pax6</i> KO pancreata.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623689, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g003", "stats"=>{"downloads"=>2, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_beta_cell_related_factors_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623689", "title"=>"Expression of beta-cell-related factors in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607255", "https://ndownloader.figshare.com/files/2607256", "https://ndownloader.figshare.com/files/2607257", "https://ndownloader.figshare.com/files/2607258", "https://ndownloader.figshare.com/files/2607259", "https://ndownloader.figshare.com/files/2607260", "https://ndownloader.figshare.com/files/2607261", "https://ndownloader.figshare.com/files/2607262", "https://ndownloader.figshare.com/files/2607263"], "description"=>"<div><p>The transcription factor <i>Pax6</i> is an important regulator of development and cell differentiation in various organs. Thus, <i>Pax6</i> was shown to promote neural development in the cerebral cortex and spinal cord, and to control pancreatic endocrine cell genesis. However, the role of <i>Pax6</i> in distinct endocrine cells of the adult pancreas has not been addressed. We report the conditional inactivation of <i>Pax6</i> in insulin and glucagon producing cells of the adult mouse pancreas. In the absence of <i>Pax6</i>, beta- and alpha-cells lose their molecular maturation characteristics. Our findings provide strong evidence that <i>Pax6</i> is responsible for the maturation of beta-, and alpha-cells, but not of delta-, and PP-cells. Moreover, lineage-tracing experiments demonstrate that <i>Pax6</i>-deficient beta- and alpha-cells are shunted towards ghrelin marked cells, sustaining the idea that ghrelin may represent a marker for endocrine cell maturation.</p></div>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623754, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0144597.s001", "https://dx.doi.org/10.1371/journal.pone.0144597.s002", "https://dx.doi.org/10.1371/journal.pone.0144597.s003", "https://dx.doi.org/10.1371/journal.pone.0144597.s004", "https://dx.doi.org/10.1371/journal.pone.0144597.s005", "https://dx.doi.org/10.1371/journal.pone.0144597.s006", "https://dx.doi.org/10.1371/journal.pone.0144597.s007", "https://dx.doi.org/10.1371/journal.pone.0144597.s008", "https://dx.doi.org/10.1371/journal.pone.0144597.s009"], "stats"=>{"downloads"=>12, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pax6_Inactivation_in_the_Adult_Pancreas_Reveals_Ghrelin_as_Endocrine_Cell_Maturation_Marker/1623754", "title"=>"<i>Pax6</i> Inactivation in the Adult Pancreas Reveals Ghrelin as Endocrine Cell Maturation Marker", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-17 08:08:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607186"], "description"=>"<p>Quantification of ghrelin<sup>+</sup> and insulin<sup>+</sup> cells in the islets of beta-cell-specific <i>Pax6</i> KO mice (Control = <i>RIP-CreER;Pax6</i><sup><i>+/+</i></sup>, KO = <i>RIP-CreER;Pax6</i><sup><i>fl/fl</i></sup>) injected at 1.5 month of age and analysed at different indicated time points post tamoxifen induction (n = 3). Error bars represent SEM; *p<0.05.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623691, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g004", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inverse_relationship_of_ghrelin_and_insulin_expression_in_the_pancreata_of_beta_cell_specific_Pax6_KO_mice_/1623691", "title"=>"Inverse relationship of ghrelin and insulin expression in the pancreata of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607187"], "description"=>"<p>Immunofluorescence staining of pancreatic cryosections from 4 week old mice at 7 days after tamoxifen induction (a-d and g-j) and 9 week old mice at 6 weeks after tamoxifen induction (e, f and k, l). (a, b) In the control islets, all of the YFP<sup>+</sup> cells express insulin. (c, d) At 7 days after tamoxifen induction few YFP<sup>+</sup><i>Pax6</i>-deficient cells are negative for insulin expression. (e, f) At 6 weeks after tamoxifen induction a majority of the YFP<sup>+</sup><i>Pax6</i>-deficient cells are negative for insulin expression. (g, h) Ghrelin<sup>+</sup> cells are not detected in the control islets. (i, j) At 7 days after tamoxifen induction few YFP<sup>+</sup><i>Pax6</i>-deficient cells express ghrelin. (k, l) At 6 weeks after tamoxifen induction a majority of the YFP<sup>+</sup><i>Pax6</i>-deficient cells express ghrelin.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623692, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gradual_decrease_in_the_population_of_insulin_expressing_cells_and_a_proportional_augmentation_in_the_population_of_ghrelin_expressing_cells_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623692", "title"=>"Gradual decrease in the population of insulin expressing cells and a proportional augmentation in the population of ghrelin expressing cells in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607188"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2.5 month old mice at 2 weeks after tamoxifen induction. Ghrelin<sup>+</sup> cells are not detected in the control islets (a-c). In the beta-cell-specific <i>Pax6</i> KO islets, ghrelin expression is up regulated (d-f) and some of the ghrelin<sup>+</sup> cells co-express insulin (d). Additionally, these ghrelin<sup>+</sup> cells co-express iAPP (e) and PC1/3 (f).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623693, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_expression_of_ghrelin_with_insulin_iAPP_and_PC1_3_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623693", "title"=>"Co-expression of ghrelin with insulin, iAPP, and PC1/3 in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607189"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2.5 month old mice at 2 weeks after tamoxifen induction. Ghrelin expression is not detected in the control islets (a-c). In beta-cell-specific <i>Pax6</i> KO islets, ghrelin expression is up regulated and ghrelin<sup>+</sup> cells are negative for <i>Pax6</i> (d) but positive for Pdx1 (e), and Nkx6.1 (f).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623694, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_beta_cell_related_transcription_factors_in_the_ghrelin_cell_population_of_beta_cell_specific_Pax6_KO_islets_/1623694", "title"=>"Expression of beta-cell-related transcription factors in the ghrelin<sup>+</sup> cell population of beta-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607196"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 4 month old mice at 6 weeks after tamoxifen induction (a-f) and 6 month old mice at 4.5 months after tamoxifen induction (g-i). Ghrelin expression is not detected in the control islets (a-c). In beta-cell-specific <i>Pax6</i> KO islets, ghrelin expression is up regulated and that of insulin down regulated in the YFP labeled <i>Pax6</i>-deficient cells (d-f). Most of the ghrelin<sup>+</sup> cells have lost the expression of insulin but some are still insulin<sup>+</sup> (arrows d-f). Some YFP<sup>+</sup> cells in the KO islets are negative for both insulin and ghrelin (arrowhead d-f). At 4.5 months after tamoxifen induction many of the YFP<sup>+</sup> cells are negative for both insulin and ghrelin (arrowheads g-i).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623696, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ghrelin_cells_originate_from_beta_cells_in_the_beta_cell_specific_Pax6_KO_islets_/1623696", "title"=>"Ghrelin cells originate from beta-cells in the beta-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607201"], "description"=>"<p>Immunofluorescence staining of pancreatic cryosections from 6 month old mice at 4.5 month after tamoxifen induction. Expression of Rfx6 (e, f) and Pdx1 (g, h) is maintained in the YFP<sup>+</sup><i>Pax6</i>-deficient cells of the beta-cell-specific <i>Pax6</i> KO islets.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623701, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g009", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_Rfx6_and_Pdx1_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623701", "title"=>"Expression of Rfx6 and Pdx1 in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607208"], "description"=>"<p>Immunofluorescence staining of pancreatic cryosections from 7 week old mice at 4 weeks after tamoxifen induction. Ki67<sup>+</sup> YFP<sup>+</sup> cells are detected in the control islets (arrows a, b) but not in the beta-cell-specific <i>Pax6</i> KO islets (c, d). On the other hand, Ki67<sup>+</sup> YFP<sup>-</sup> cells are detected in both the control and KO islets (arrowhead a-d). Quantification of Ki67<sup>+</sup> YFP<sup>+</sup> cells (e) in the islets of 7 week old mice at 4 weeks after tamoxifen induction (n = 3). Error bars represent SEM; *p<0.05.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623708, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g010", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pax6_deficient_beta_cells_do_not_proliferate_/1623708", "title"=>"<i>Pax6</i>-deficient beta-cells do not proliferate.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607212"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2 month old mice at 4 weeks after tamoxifen induction. In beta-cell-specific <i>Pax6</i> KO islets, C-peptide expression is lost from majority of the YFP<sup>+</sup><i>Pax6</i>-deficient cells (d). However, PC1/3 (e) and PC2 (f) expression is maintained in the YFP<sup>+</sup><i>Pax6</i>-deficient cells.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623712, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g011", "stats"=>{"downloads"=>4, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_C_peptide_PC1_3_and_PC2_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623712", "title"=>"Expression of C-peptide, PC1/3, and PC2 in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607214"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 4 month old mice at 6 weeks after tamoxifen induction. In the control islets, expression of proSAAS and 7B2 is low in the YFP labeled beta-cells (a-d). In beta-cell-specific <i>Pax6</i> KO islets, expression of both proSAAS and 7B2 is highly up regulated in the YFP<sup>+</sup><i>Pax6</i>-deficient cells (e-h).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623714, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g012", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_proSAAS_and_7B2_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623714", "title"=>"Expression of proSAAS and 7B2 in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607215"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 2 month old mice at 4 weeks after tamoxifen induction. In the control islets, expression of Glut2 is detected in both YFP<sup>+</sup> and YFP<sup>-</sup> insulin<sup>+</sup> cells (a-c). In the beta-cell-specific <i>Pax6</i> KO islets, Glut2 expression is lost in the YFP labeled <i>Pax6</i>-deficient cells as well as in a majority of the YFP<sup>-</sup> insulin<sup>+</sup> cells (arrows d-f). Rarely, some YFP<sup>-</sup> insulin<sup>+</sup> cells do express Glut2 in the KO islets (arrowhead d-f).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623715, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g013", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_Glut2_expression_due_to_direct_and_or_indirect_effect_of_Pax6_ablation_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623715", "title"=>"Loss of Glut2 expression due to direct and/or indirect effect of <i>Pax6</i> ablation in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-18 08:42:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607216"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 4 month old mice at 6 weeks after tamoxifen induction. GLP-1 receptor is expressed in both YFP<sup>+</sup> and YFP<sup>-</sup> insulin<sup>+</sup> cells in the control islets (a-d). In beta-cell-specific <i>Pax6</i> KO islets, GLP-1 receptor expression is lost from the YFP labeled <i>Pax6</i>-deficient cells (arrowheads e-h) but maintained in the YFP<sup>-</sup> insulin<sup>+</sup> cells (arrows e-h).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623716, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g014", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_GLP_1_receptor_in_the_islets_of_beta_cell_specific_Pax6_KO_mice_/1623716", "title"=>"Expression of GLP-1 receptor in the islets of beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607217"], "description"=>"<p>Measurement of blood glucose level in mice after tamoxifen induction at 3 weeks (a) or 1.5 month (b) (n = 5). Increase in blood glucose level is observed at either age but a slight decrease in the long term is only seen in young mice (a). Quantification of insulin<sup>+</sup> YFP<sup>-</sup>, YFP<sup>+</sup> insulin<sup>-</sup>, and insulin<sup>+</sup> YFP<sup>+</sup> cells in the islets of 13 week old mice at 10 weeks after tamoxifen induction (c) and 6 month old mice at 4.5 month after tamoxifen induction (d) (n = 3). Number of insulin<sup>+</sup> YFP<sup>-</sup> cells is increased at either age indicating some beta-cell regeneration. Due to the loss of insulin expression in YFP labeled <i>Pax6</i>-deficient cells, a significant increase in the number of YFP<sup>+</sup> insulin<sup>-</sup> and a decrease in the number of YFP<sup>+</sup> insulin<sup>+</sup> cells is also observed in the KO islets. (Control = <i>RIP-CreER;R26-YFP;Pax6</i><sup><i>+/+</i></sup>, Pax6 KO = <i>RIP-CreER;R26-YFP;Pax6</i><sup><i>fl/fl</i></sup>). Error bars represent SEM; *p<0.05.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623717, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g015", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Development_of_hyperglycemia_and_resulting_beta_cell_regeneration_in_the_beta_cell_specific_Pax6_KO_mice_/1623717", "title"=>"Development of hyperglycemia and resulting beta-cell regeneration in the beta-cell-specific <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607218"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 1 month old mice. In control islets, all the YFP<sup>+</sup> cells express <i>Pax6</i> and glucagon (a-c). In alpha-cell-specific <i>Pax6</i> KO islets, most of the YFP<sup>+</sup> cells are negative for <i>Pax6</i> and have lost the expression of glucagon as well (d-f). YFP<sup>-</sup> glucagon<sup>+</sup> cells in the KO islets express <i>Pax6</i> (arrowheads d-f). Rarely YFP<sup>+</sup> glucagon<sup>+</sup><i>Pax6<sup>-</sup></i> cells are also found in the KO islets (arrows d-f). Quantification of YFP<sup>+</sup> glucagon<sup>+</sup> cells in relation to total glucagon<sup>+</sup> cells in 1 month old non-inducible alpha-cell-specific control (<i>Glu-Cre;R26-YFP;Pax6</i><sup><i>+/+</i></sup>) mice, and in Dox-inducible alpha-cell-specific control (<i>Glu-rtTA;TetO-Cre;R26-YFP;Pax6</i><sup><i>+/+</i></sup>) mice at 4 months of age following 6 weeks of Doxycycline treatment (g) (n = 3). Nearly 68% and 75% of the glucagon<sup>+</sup> cells are labeled with YFP in non-inducible and Dox-inducible alpha-cell-specific control mice, respectively. Error bars represent SEM.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623718, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g016", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alpha_cell_specific_ablation_of_Pax6_/1623718", "title"=>"Alpha-cell-specific ablation of <i>Pax6</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607221"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 1 month old mice. Ghrelin expression is not detected in the control islets (a-c). In alpha-cell-specific <i>Pax6</i> KO islets ghrelin expression is up regulated in YFP labeled cells (d-f) and rarely ghrelin expression co-localizes with glucagon expression (arrows d-f).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623721, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g017", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ghrelin_cells_originate_from_alpha_cells_in_the_alpha_cell_specific_Pax6_KO_islets_/1623721", "title"=>"Ghrelin<sup>+</sup> cells originate from alpha-cells in the alpha-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607225"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from 1 month old mice. Ghrelin expression is not detected in the control islets (a-c). In alpha-cell-specific <i>Pax6</i> KO islets ghrelin expression is up regulated in YFP labeled cells and ghrelin<sup>+</sup> cells are negative for Pax6 (d) and MafB (e) expression but positive for Arx (f) expression.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623724, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g018", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_alpha_cell_related_transcription_factors_in_ghrelin_cells_of_alpha_cell_specific_Pax6_KO_islets_/1623724", "title"=>"Expression of alpha-cell-related transcription factors in ghrelin<sup>+</sup> cells of alpha-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607231"], "description"=>"<p>Immunofluorescence staining of pancreatic cryosections from 1 month old mice. 7B2 expression is very low in the control islets (a, b). In alpha-cell-specific <i>Pax6</i> KO islets, 7B2 expression is highly up regulated in YFP labeled <i>Pax6</i>-deficient cells (e, f). Compared to control islets PC2 expression is unchanged in the alpha-cell-specific <i>Pax6</i> KO islets (c, d and g, h).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623730, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g019", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_7B2_and_PC2_in_alpha_cell_specific_Pax6_KO_islets_/1623730", "title"=>"Expression of 7B2 and PC2 in alpha-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607234"], "description"=>"<p>Quantification of total glucagon<sup>+</sup> cell population in non-inducible alpha-cell-specific <i>Pax6</i> KO islets at 1 month, 3 months, and 8 months of age, and in Dox-inducible alpha-cell-specific <i>Pax6</i> KO islets at 4 months of age following 6 weeks of Doxycycline treatment (a) (n = 3). Number of total glucagon<sup>+</sup> cells is unchanged at the younger age but significantly reduced at 8 months of age in the KO islets. Quantification of glucagon<sup>+</sup> YFP<sup>-</sup>, YFP<sup>+</sup> glucagon<sup>-</sup>, and YFP<sup>+</sup> glucagon<sup>+</sup> cells in Dox-inducible alpha-cell-specific <i>Pax6</i> KO islets at 4 months of age following 6 weeks of Doxycycline treatment (b) and in the non-inducible alpha-cell-specific <i>Pax6</i> KO islets at 1 month, 3 months, and 8 months of age (c) (n = 3). Number of glucagon<sup>+</sup> YFP<sup>-</sup> cells is significantly increased in the Dox-inducible KO islets as well as in the non-inducible KO islets at 1 month and 3 months of age but not at 8 months of age. Due to the loss of glucagon expression in YFP labeled <i>Pax6</i>-deficient cells, a significant increase in the number of YFP<sup>+</sup> glucagon<sup>-</sup> and a decrease in the number of YFP<sup>+</sup> glucagon<sup>+</sup> cells is also observed at all stages and in both types of islets. (Non-inducible control = <i>Glu-Cre;R26-YFP;Pax6</i><sup><i>+/+</i></sup>, Non-inducible <i>Pax6</i> KO = <i>Glu-Cre;R26-YFP;Pax6</i><sup><i>fl/fl</i></sup>, Dox-inducible control = <i>Glu-rtTA;TetO-Cre;R26-YFP; Pax6</i><sup><i>+/+</i></sup>, Dox-inducible <i>Pax6</i> KO = <i>Glu-rtTA;TetO-Cre;R26-YFP;Pax6</i><sup><i>fl/fl</i></sup>). Error bars represent SEM; *p<0.05.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623733, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g020", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Alpha_cell_neogenesis_in_the_alpha_cell_specific_Pax6_KO_islets_/1623733", "title"=>"Alpha-cell neogenesis in the alpha-cell-specific <i>Pax6</i> KO islets.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607237"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from mice that were injected with tamoxifen at 2 months of age and analysed at 1 week post tamoxifen induction. A nearly 100% ablation of <i>Pax6</i> was confirmed in the islets of ubiquitous <i>Pax6</i> KO mice (c, d).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623736, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g021", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ubiquitous_ablation_of_Pax6_/1623736", "title"=>"Ubiquitous ablation of <i>Pax6</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607169"], "description"=>"<p>Age at tamoxifen induction and analysis time point post-induction is indicated. After each timeline, the respective figure number is also mentioned.</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623677, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g001", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Different_experimental_time_lines_used_for_the_beta_cell_specific_Pax6_ablation_/1623677", "title"=>"Different experimental time lines used for the beta-cell-specific <i>Pax6</i> ablation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2607243"], "description"=>"<p>Double immunofluorescence staining of pancreatic cryosections from mice that were injected with tamoxifen at 2 months of age and analysed at 1 week, 2 weeks, and 3 weeks post tamoxifen induction. Ghrelin<sup>+</sup> cells are not detected in the control islets (a-d). In the ubiquitous <i>Pax6</i> KO islets, ghrelin expression is up regulated (e-p). Ghrelin expression shows co-localization with that of glucagon (e, i, m) and insulin (f, j, n) but never with that of somatostatin (g, k, o) and PP (h, l, p). In ubiquitous <i>Pax6</i> KO islets, a loss of glucagon (e, i, m) and insulin expression (f, j, n) was observed but not that of somatostatin (g, k, o) and PP (h, l, p). Furthermore, glucagon<sup>+</sup> cells were the first ones to be affected in relation to the loss of glucagon expression and upregulation of ghrelin expression (e, i, m). (TI = Tamoxifen induction).</p>", "links"=>[], "tags"=>["Endocrine Cell Maturation Marker", "PAX 6", "adult mouse pancreas", "transcription factor PAX 6", "maturation", "Pax 6 Inactivation", "beta"], "article_id"=>1623742, "categories"=>["Biological Sciences"], "users"=>["Zeeshan Ahmad", "Maria Rafeeq", "Patrick Collombat", "Ahmed Mansouri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0144597.g022", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variable_effect_of_Pax6_ablation_in_the_islets_of_adult_ubiquitous_Pax6_KO_mice_/1623742", "title"=>"Variable effect of <i>Pax6</i> ablation in the islets of adult-ubiquitous <i>Pax6</i> KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-17 08:08:51"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2021", "month"=>"1"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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