HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst
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{"title"=>"HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst", "type"=>"journal", "authors"=>[{"first_name"=>"Eryn", "last_name"=>"Wicklow", "scopus_author_id"=>"56398494700"}, {"first_name"=>"Stephanie", "last_name"=>"Blij", "scopus_author_id"=>"55383733900"}, {"first_name"=>"Tristan", "last_name"=>"Frum", "scopus_author_id"=>"36478458000"}, {"first_name"=>"Yoshikazu", "last_name"=>"Hirate", "scopus_author_id"=>"55624468200"}, {"first_name"=>"Richard A.", "last_name"=>"Lang", "scopus_author_id"=>"7402128963"}, {"first_name"=>"Hiroshi", "last_name"=>"Sasaki", "scopus_author_id"=>"55248695700"}, {"first_name"=>"Amy", "last_name"=>"Ralston", "scopus_author_id"=>"8564764500"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"25340657", "doi"=>"10.1371/journal.pgen.1004618", "sgr"=>"84907735517", "isbn"=>"1553-7404", "scopus"=>"2-s2.0-84907735517", "issn"=>"15537404", "pui"=>"600311100"}, "id"=>"18274c1b-659c-3fc5-8b73-db58d9a48bbf", "abstract"=>"Pluripotent epiblast (EPI) cells, present in the inner cell mass (ICM) of the mouse blastocyst, are progenitors of both embryonic stem (ES) cells and the fetus. Discovering how pluripotency genes regulate cell fate decisions in the blastocyst provides a valuable way to understand how pluripotency is normally established. EPI cells are specified by two consecutive cell fate decisions. The first decision segregates ICM from trophectoderm (TE), an extraembryonic cell type. The second decision subdivides ICM into EPI and primitive endoderm (PE), another extraembryonic cell type. Here, we investigate the roles and regulation of the pluripotency gene Sox2 during blastocyst formation. First, we investigate the regulation of Sox2 patterning and show that SOX2 is restricted to ICM progenitors prior to blastocyst formation by members of the HIPPO pathway, independent of CDX2, the TE transcription factor that restricts Oct4 and Nanog to the ICM. Second, we investigate the requirement for Sox2 in cell fate specification during blastocyst formation. We show that neither maternal (M) nor zygotic (Z) Sox2 is required for blastocyst formation, nor for initial expression of the pluripotency genes Oct4 or Nanog in the ICM. Rather, Z Sox2 initially promotes development of the primitive endoderm (PE) non cell-autonomously via FGF4, and then later maintains expression of pluripotency genes in the ICM. The significance of these observations is that 1) ICM and TE genes are spatially patterned in parallel prior to blastocyst formation and 2) both the roles and regulation of Sox2 in the blastocyst are unique compared to other pluripotency factors such as Oct4 or Nanog.", "link"=>"http://www.mendeley.com/research/hippo-pathway-members-restrict-sox2-inner-cell-mass-it-promotes-icm-fates-mouse-blastocyst", "reader_count"=>95, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>7, "Researcher"=>20, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>30, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>2, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>7, "Researcher"=>20, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>30, "Student > Postgraduate"=>4, "Student > Master"=>15, "Other"=>2, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>36, "Agricultural and Biological Sciences"=>50, "Medicine and Dentistry"=>4, "Physics and Astronomy"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>50}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>36}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Puerto Rico"=>1, "Netherlands"=>1, "United States"=>2, "Japan"=>2, "Denmark"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1760622"], "description"=>"<p>A) Immunofluorescent analysis of SOX2 and NANOG shows that SOX2 is detected specifically in ICM cells at the 16-cell stage and later, while NANOG is detected in all cells at these stages. B) SOX2 is not upregulated in the TE of <i>Cdx2</i> null embryos at early or late blastocyst stages, indicating that CDX2 does not restrict SOX2 to the ICM. C) SOX2 is ectopically expressed in outside cells of embryos lacking the HIPPO pathway member <i>Tead4</i> (asterisk  =  SOX2-positive outside cell). TE cells are defined both by outside position and by basolateral localization of E-CADHERIN (ECAD). D) Either <i>Lats2</i> or <i>β-Globin</i> mRNAs were injected into both cells of 2-cell embryos, and embryos were then cultured to blastocyst stage. E) The proportion of outside cells in which SOX2 was ectopically expressed was significantly increased in both <i>Tead4</i> null embryos, and in embryos overexpressing the HIPPO pathway member <i>Lats2</i>, relative to controls (p-value calculated by t-test). F) Overexpression of <i>Lats2</i>, which prevents nuclear YAP localization, causes ectopic expression of SOX2 in outside cells (indicated by asterisk). In all panels, bar  = 20 µm.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1219584, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g001", "stats"=>{"downloads"=>1, "page_views"=>142, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SOX2_is_restricted_to_ICM_progenitors_by_HIPPO_pathway_members_and_not_by_CDX2_/1219584", "title"=>"SOX2 is restricted to ICM progenitors by HIPPO pathway members and not by CDX2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 16:28:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1760747"], "description"=>"<p>A) Expression of <i>Fgf4</i>, as measured by qPCR, is reduced in the absence of <i>Sox2</i>. B) Treatment scheme and evidence that resultant embryos are equivalent in cell number to developmental stage E3.75. C) FGF4/HEP treatment is sufficient to induce expression of SOX17 in <i>Sox2</i> null embryos. D) Quantification of the experiment shown in panel C. E) Overview of strategy to generate chimeric embryos and evidence that chimeras are equivalent in cell number to E3.75 (avg. no. host cells per ICM: untreated nonmutant: 19.1+/−6.2; untreated <i>Sox2</i> null: 20.0+/−4.1; treated nonmutant: 11.2+/−3.6; treated <i>Sox2</i> null: 12.0+/−3.2). F) Wild-type ES cells rescue expression of SOX17 in <i>Sox2</i> null embryos. G) Chimeras from panel F. Bar  = 20 µm, p-value calculated by t-test; ANOVA performed for panels B, D, E; n.s.  = p>0.05.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1219614, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g005", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sox2_promotes_PE_development_non_cell_autonomously_via_FGF4_/1219614", "title"=>"<i>Sox2</i> promotes PE development non cell-autonomously via FGF4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 16:28:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1770343", "https://ndownloader.figshare.com/files/1770344", "https://ndownloader.figshare.com/files/1770345", "https://ndownloader.figshare.com/files/1770346", "https://ndownloader.figshare.com/files/1770347"], "description"=>"<div><p>Pluripotent epiblast (EPI) cells, present in the inner cell mass (ICM) of the mouse blastocyst, are progenitors of both embryonic stem (ES) cells and the fetus. Discovering how pluripotency genes regulate cell fate decisions in the blastocyst provides a valuable way to understand how pluripotency is normally established. EPI cells are specified by two consecutive cell fate decisions. The first decision segregates ICM from trophectoderm (TE), an extraembryonic cell type. The second decision subdivides ICM into EPI and primitive endoderm (PE), another extraembryonic cell type. Here, we investigate the roles and regulation of the pluripotency gene <i>Sox2</i> during blastocyst formation. First, we investigate the regulation of <i>Sox2</i> patterning and show that SOX2 is restricted to ICM progenitors prior to blastocyst formation by members of the HIPPO pathway, independent of CDX2, the TE transcription factor that restricts <i>Oct4</i> and <i>Nanog</i> to the ICM. Second, we investigate the requirement for <i>Sox2</i> in cell fate specification during blastocyst formation. We show that neither maternal (M) nor zygotic (Z) <i>Sox2</i> is required for blastocyst formation, nor for initial expression of the pluripotency genes <i>Oct4</i> or <i>Nanog</i> in the ICM. Rather, Z <i>Sox2</i> initially promotes development of the primitive endoderm (PE) non cell-autonomously via FGF4, and then later maintains expression of pluripotency genes in the ICM. The significance of these observations is that 1) ICM and TE genes are spatially patterned in parallel prior to blastocyst formation and 2) both the roles and regulation of <i>Sox2</i> in the blastocyst are unique compared to other pluripotency factors such as <i>Oct4</i> or <i>Nanog</i>.</p></div>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1221713, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004618.s001", "https://dx.doi.org/10.1371/journal.pgen.1004618.s002", "https://dx.doi.org/10.1371/journal.pgen.1004618.s003", "https://dx.doi.org/10.1371/journal.pgen.1004618.s004", "https://dx.doi.org/10.1371/journal.pgen.1004618.s005"], "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIPPO_Pathway_Members_Restrict_SOX2_to_the_Inner_Cell_Mass_Where_It_Promotes_ICM_Fates_in_the_Mouse_Blastocyst_/1221713", "title"=>"HIPPO Pathway Members Restrict SOX2 to the Inner Cell Mass Where It Promotes ICM Fates in the Mouse Blastocyst", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-10-23 13:43:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1769848"], "description"=>"<p>A) By E4.25, expression of PE genes, including SOX17, PDGFRA, and GATA4, is restored in <i>Sox2</i> null embryos, but the ICM appears disorganized relative to control embryos. (arrowheads  =  mislocalized PE cells. B) In <i>Sox2</i> null embryos, the average proportion of ICM cells expressing SOX17 increases progressively, catching up with control embryos by E4.25. C) Quantification of the average number of apoptotic cells in wild type and <i>Sox2</i> null embryos at the indicated time points. D) At E4.25, the expression of SOX17 in <i>Sox2</i> null embryos depends on FGFR/MEK. E) At E4.25, SOX7, a marker of mature PE, is detectable in the absence of <i>Sox2</i>. F) At E4.25, expression of LAMA1 and DAB2 are reduced in the absence of <i>Sox2</i>, consistent with defects in PE localization. G) At E4.25, expression of OCT4, PECAM1, and NANOG are reduced in the absence of <i>Sox2</i>. Bar  = 20 µm, p-value calculated by t-test; n.s.  = p>0.05.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1221647, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g006", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sox2_is_required_to_maintain_expression_EPI_but_not_most_PE_genes_/1221647", "title"=>"<i>Sox2</i> is required to maintain expression EPI, but not most PE genes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 10:24:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1770338"], "description"=>"<p>A) At the 16-cell stage, when ICM progenitors first arise, HIPPO pathway members regulate expression of TE (<i>Cdx2</i>) and ICM (<i>Sox2</i>) genes in parallel. At this stage, OCT4 and NANOG are still expressed ubiquitously. B) In the blastocyst, <i>Sox2</i> expression is restricted to EPI cells by FGFR/MEK signaling. In EPI cells, SOX2 helps promote expression of <i>Fgf4</i>, which signals to neighboring cells to induce expression of PE genes. In PE cells, MAPK promotes PE gene expression in an <i>Oct4</i>-dependent manner <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004618#pgen.1004618-Frum1\" target=\"_blank\">[3]</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004618#pgen.1004618-Aksoy1\" target=\"_blank\">[13]</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004618#pgen.1004618-LeBin1\" target=\"_blank\">[59]</a>, and represses expression of <i>Sox2</i> and <i>Nanog</i> in PE cells either directly or indirectly. C) In the late blastocyst, SOX2 helps maintain expression of pluripotency genes, and FGF4, or other signals from EPI, maintain expression of PE genes in neighboring cells.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1221707, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g007", "stats"=>{"downloads"=>0, "page_views"=>48, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_roles_and_regulation_of_SOX2_during_blastocyst_formation_/1221707", "title"=>"The roles and regulation of SOX2 during blastocyst formation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 13:43:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/1760710"], "description"=>"<p>A) At E3.75, NANOG is detected in <i>Sox2</i> null embryos, but SOX17 is not detected in most <i>Sox2</i> null embryos (arrowhead  =  ICM cell expressing neither NANOG nor SOX17). B) At E3.75, the average proportion of ICM cells in which NANOG is elevated is equivalent among all genotypes examined, indicating that <i>Sox2</i> is not required for expression of NANOG in the ICM. However, the average proportion of ICM cells in which SOX17 is detected is significantly reduced, and the proportion of ICM cells in which neither NANOG nor SOX17 are detected is significantly increased, in the absence of either Z or MZ <i>Sox2</i>. C) At E3.75, <i>Sox2</i> is required for high levels of GATA6 in PE cells. D) Quantification of immunofluorescent results showing that the proportion of ICM cells in which high levels of GATA6 are detected is significantly lower <i>Sox2</i> null embryos at E3.75, while the proportion of ICM cells expressing both NANOG and low levels of GATA6 is significantly higher. E) Expression of PDGFRA in the ICM depends on <i>Sox2</i>. F) Expression of GATA4 in the ICM depends on <i>Sox2</i>. Bar  = 20 µm, p-value calculated by t-test in B, and by Chi-squared test in E; n.s.  = p>0.05.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1219609, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g004", "stats"=>{"downloads"=>2, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sox2_is_required_for_the_initial_expression_of_PE_genes_in_the_ICM_/1219609", "title"=>"<i>Sox2</i> is required for the initial expression of PE genes in the ICM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 16:28:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1760659"], "description"=>"<p>A) qPCR analysis confirms that <i>Sox2</i> is deleted in oocytes from females carrying <i>Zp3Cre</i> and the floxed <i>Sox2</i> allele (bars represent standard deviation from the average of 3 replicate pools of ∼10 oocytes each). B) M <i>Sox2</i> is not required for development because litter sizes did not significantly differ between non-mutant females, and females in which <i>Sox2</i> had been deleted in the germ line. C) The expression patterns of the TE markers CDX2 and EOMES and the ICM marker OCT4 are normal in embryos lacking <i>Sox2</i>. D) The number of total cells, inside (ICM) cells, and outside (TE) cells is normal in the absence of M, Z, or MZ <i>Sox2</i>. Bar  = 20 µm, p-value calculated by t-test in A, B; ANOVA performed in D; n.s.  = p>0.05.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1219594, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g002", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sox2_is_not_required_for_the_first_lineage_decision_segregation_of_ICM_and_TE_cell_types_/1219594", "title"=>"<i>Sox2</i> is not required for the first lineage decision: segregation of ICM and TE cell types.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 16:28:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1760673"], "description"=>"<p>A) In wild-type (WT) embryos at early E3.75, NANOG is detected in a salt-and-pepper pattern in the ICM, while SOX2 begins to be downregulated in PE cells (arrowhead: cell in which NANOG is already downregulated, but SOX2 is not yet downregulated). B) In WT embryos at late E3.75, SOX2 and SOX17 are detected in a salt-and-pepper pattern in the ICM. C) At E4.25, SOX2 is exclusively detected in EPI and SOX17 in PE. D) At E3.75, SOX2 is detected in a larger proportion of ICM cells than is NANOG, indicating that NANOG is downregulated in the PE slightly before SOX2. E) FGF4/HEP is sufficient to repress SOX2 expression in the ICM since the SOX2-expressing proportion of ICM cells is reduced (and GATA6-expressing proportion concomitantly expanded) in wild-type embryos incubated in FGF4/HEP (avg. no. untreated ICM cells: 25.6+/−3.8; avg. no. treated ICM cells: 30.4+/−7.2). F) The downregulation of SOX2 in PE cells is dependent on FGFR/MEK, since the proportion of ICM cells expressing SOX2 is expanded (and the SOX17-expressing proportion concomitantly reduced) in wild-type embryos incubated in inhibitors of FGFR/MEK (avg. no. untreated ICM cells: 19.4+/−5.1; avg. no. treated ICM cells: 13+/−4.1). Bar  = 20 µm, p-value calculated by t-test.</p>", "links"=>[], "tags"=>["epi", "Mouse Blastocyst Pluripotent epiblast", "Sox 2", "cell fate decisions", "TE transcription factor", "fgf", "blastocyst formation", "Oct 4", "cell fate specification", "HIPPO Pathway Members", "pe", "es", "extraembryonic cell type", "Promotes ICM Fates", "Sox 2 patterning", "Inner Cell Mass", "pluripotency genes", "cdx", "pluripotency gene Sox 2", "decision segregates ICM", "pluripotency genes Oct 4", "decision subdivides ICM", "Z Sox 2"], "article_id"=>1219602, "categories"=>["Uncategorised"], "users"=>["Eryn Wicklow", "Stephanie Blij", "Tristan Frum", "Yoshikazu Hirate", "Richard A. Lang", "Hiroshi Sasaki", "Amy Ralston"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004618.g003", "stats"=>{"downloads"=>1, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sox2_is_restricted_to_EPI_progenitors_through_an_Fgf4_MEK_dependent_mechanism_/1219602", "title"=>"<i>Sox2</i> is restricted to EPI progenitors through an Fgf4/MEK-dependent mechanism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-10-23 16:28:02"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
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  • {"unique-ip"=>"24", "full-text"=>"26", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
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  • {"unique-ip"=>"25", "full-text"=>"31", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"23", "full-text"=>"25", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"13", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"26", "full-text"=>"24", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"23", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
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  • {"unique-ip"=>"20", "full-text"=>"19", "pdf"=>"10", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"13", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
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  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
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  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
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  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
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  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
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Relative Metric

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