{"id":106749,"date":"2011-11-02T00:00:00","date_gmt":"2011-11-02T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/evolution-of-embryonic-pluripotency\/"},"modified":"2011-11-02T00:00:00","modified_gmt":"2011-11-02T00:00:00","slug":"evolution-of-embryonic-pluripotency","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/evolution-of-embryonic-pluripotency\/","title":{"rendered":"\u00abevolution of embryonic pluripotency\u00bb"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Beatriz Fernandez-tresguerres Torrecillas <\/strong><\/h2>\n<p>Pluripotency in the early mouse is established and maintained by a gene regulatory  network under the control of a core set of transcription factors that includes oct4,  sox2 and nanog. This network is shared by the embryonic stem cells which can give  rise to any adult cell type thanks in part to this network, which shuts down the cells\u00c2\u00bf  differentiation programs and keeps them in an undifferentiated state. While the  network is largely conserved in eutherian mammals, very little information is available  regarding its evolutionary conservation in other vertebrates. We have compared the  embryonic pluripotency networks in mouse and chick by means of expression analysis  in the pre-gastrulation chick embryo, genomic comparisons, functional assays of  pluripotency-related regulatory elements in es cells and blastocysts, and in vivo  overexpression assays. We find that multiple components of the network are either  novel to mammals or have acquired novel expression domains in early developmental  stages of the mouse. We also find that the downstream action of the mouse core  pluripotency factors is largely mediated by genomic sequence elements that are not  conserved with chick. In the case of  sox2  and  fgf4, we find that elements driving  expression in embryonic pluripotent cells have evolved  through a small number of  nucleotide changes that created novel binding sites for core factors.  these findings suggest that the ep-grn arose not only  through the appearance of  novel pluripotency genes but also by co-opting and duplicating existing  genes and  establishing new regulatory interactions between them.  The  de novo  appearance of  some of these interactions in mammals was confirmed by overexpressing nanog in  chick and mouse embryos. Furthermore, expression analysis of these embryos  suggests additional conserved roles for  nanog as a repressor of neural and  haematopoietic differentiation at gastrulation stages. our results show that the network in charge of embryonic pluripotency is an  evolutionary novelty of mammals that may have evolved owing to the comparatively  extended period during which mammalian embryonic cells need to be maintained in  an undetermined state prior to  differentiation. Further knowledge of how this  embryonic pluripotency changed during evolution will provide a deeper understanding  of its control and it will extend our  ability to exploit the potential  of stem cells.   la pluripotencia en el embri\u00f3n temprano de rat\u00f3n la establece y mantiene una red  g\u00e9nica regulatoria bajo el control de un grupo central de factores de transcripci\u00f3n que  incluye oct4, sox2 y nanog. Esta red la comparten las c\u00e9lulas madre embrionarias que  pueden dar lugar a cualquier tipo de c\u00e9lula adulta gracias en parte a que esta red act\u00faa  bloqueando los programas celulares de diferenciaci\u00f3n mientras mantiene a las c\u00e9lulas  en un estado indiferenciado. Esta red est\u00e1 ampliamente conservada en mam\u00edferos  euterios pero poco se sabe de su conservaci\u00f3n evolutiva en otros vertebrados. Hemos  comparado las redes de pluripotencia embrionaria de rat\u00f3n y pollo por medio de  an\u00e1lisis de expresi\u00f3n del embri\u00f3n de pollo pre-gastrulatorio, comparaciones  gen\u00f3micas, ensayos funcionales con los elementos reguladores relacionados con la  pluripotencia en c\u00e9lulas madre y blastocistos, as\u00ed como por ensayos de sobreexpresi\u00f3n  in vivo. Hemos encontrado que m\u00faltiples componentes de la red son nuevos en  mam\u00edferos o han adquirido nuevos dominios de expresi\u00f3n en los estadios tempranos  del desarrollo del rat\u00f3n. Tambi\u00e9n que la acci\u00f3n downstream de los factores centrales  de pluripotencia en rat\u00f3n, esta mediada por elementos de secuencia gen\u00f3mica que no  est\u00e1n conservados en pollo. En el caso de sox2 y fgf4 encontramos que elementos que  dirigen la expresi\u00f3n en las c\u00e9lulas embrionarias pluripotentes evolucionaron por un  peque\u00f1o n\u00famero de cambios en los nucle\u00f3tidos que crearon nuevos sitios de uni\u00f3n  para los factores centrales. Estos resultados sugieren que la red regulatoria g\u00e9nica de  la pluripotencia embrionaria surgi\u00f3 no solo por la aparici\u00f3n de nuevos genes sino  tambi\u00e9n por cooptaci\u00f3n y duplicaci\u00f3n de genes ya existentes y por la aparici\u00f3n de  nuevas interacciones entre ellos. De hecho sobreexpresando nanog en embriones de  pollo y rat\u00f3n confirmamos que algunas interacciones son nuevas en este \u00faltimo. Por  otra parte, el an\u00e1lisis de expresi\u00f3n de estos embriones sugiere que nanog tiene un  papel adicional y conservado como represor de diferenciaci\u00f3n neural y  hematopoy\u00e9tica en estad\u00edos gastrulatorios. Los resultados muestran que la red  encargada de la pluripotencia embrionaria es una novedad evolutiva de mam\u00edferos  que  surgi\u00f3  quiz\u00e1 porque \u00e9stos necesitaban de un mantenimiento del estado  indeterminado de las c\u00e9lulas embrionarias mucho m\u00e1s prolongado que otros  vertebrados. Un mayor conocimiento de c\u00f3mo la pluripotencia embrionaria ha  evolucionado nos ayudar\u00e1 a comprender en profundidad su control y a entender y usar  todo el potencial de las c\u00e9lulas madre.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>\u00abevolution of embryonic pluripotency\u00bb<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 \u00abevolution of embryonic pluripotency\u00bb <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Beatriz Fernandez-tresguerres Torrecillas <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 11\/02\/2011<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Miguel Manzanares Fourcade<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: fernando Gir\u00e1ldez orgaz <\/li>\n<li>Manuel Serrano marug\u00e1n (vocal)<\/li>\n<li>trist\u00e1n Rodrigu\u00e9z farningham (vocal)<\/li>\n<li>angel Raya chamorro (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Beatriz Fernandez-tresguerres Torrecillas Pluripotency in the early mouse is established and maintained by a gene regulatory network [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[1],"tags":[27476,214711,12616,41977,56094,146549],"class_list":["post-106749","post","type-post","status-publish","format-standard","hentry","category-sin-categoria","tag-angel-raya-chamorro","tag-beatriz-fernandez-tresguerres-torrecillas","tag-fernando-giraldez-orgaz","tag-manuel-serrano-marugan","tag-miguel-manzanares-fourcade","tag-tristan-rodriguez-farningham"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/106749","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=106749"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/106749\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=106749"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=106749"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=106749"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}