CEBPa is an orchestrator of trophectoderm specification
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Document Version
Author
Director
Graf, Thomas
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Publication Date
Pages
116 p.
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Citation
Wei, X. CEBPa is an orchestrator of trophectoderm specification. Universitat Pompeu Fabra; 2024. handle: http://hdl.handle.net/10803/692658
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Citation
Doctoral program
Programa de Doctorat en Biomedicina
Abstract
La bifurcación entre trofoectodermo y la masa celular interna es la decisión de desarrollo más temprana, pero cómo se inicia y en qué etapa embrionaria ocurre no se entiende completamente. Aquí describimos que el factor de transcripción CEBPa es un regulador temprano que influye en esta bifurcación. El factor se expresa en embriones de 4 y 8 células y en el trofoectodermo de los blastocistos. Su eliminación por knockout cigótico provocó un retraso en la formación del blastocisto y una disminución en la proporción de células del trofoectodermo. La expresión ectópica de CEBPa en células madre embrionarias es suficiente para inducir células similares al trofoectodermo al alterar la accesibilidad de los elementos reguladores génicos (ERGs), lo que conduce a la activación de genes específicos del trofoectodermo y el silenciamiento de genes específicos de células madre embrionarias. Un conjunto de ERGs del trofoectodermo se vuelven accesibles en embriones de 4 y 8 células, coincidiendo con la expresión de CEBPa y su unión a estas regiones potenciadoras. Por lo tanto, CEBPa podría dotar a los blastómeros de los embriones de 4 a 8 células de las herramientas necesarias para convertirlos en trofoectodermo en un futuro, sentando las bases para la bifurcación del desarrollo.
The bifurcation between trophectoderm and inner cell mass (ICM) is the earliest developmental decision yet how it is initiated and at which embryonic stage is incompletely understood. Here we describe that the transcription factor CEBPa is an orchestrator of this bifurcation. It is expressed in 4- and 8-cell embryos and in the trophectoderm layer of blastocysts. Its zygotic knockout caused a delay in blastocyst formation and a decrease in the proportion of trophectoderm cells. Ectopic CEBPa expression in embryonic stem cells suffices to induce trophectoderm-like cells by altering the accessibility of gene regulatory elements (GREs), leading to the activation of TE-specific genes and silencing of ESC-specific genes. A cohort of trophectoderm GREs become accessible in 4- and 8-cell embryos, coinciding with CEBPa expression and binding to these enhancer regions. CEBPa may thus equip totipotent blastomeres of 4- to 8-cell embryos with future trophectoderm competence, setting the stage for the earliest developmental bifurcation.
The bifurcation between trophectoderm and inner cell mass (ICM) is the earliest developmental decision yet how it is initiated and at which embryonic stage is incompletely understood. Here we describe that the transcription factor CEBPa is an orchestrator of this bifurcation. It is expressed in 4- and 8-cell embryos and in the trophectoderm layer of blastocysts. Its zygotic knockout caused a delay in blastocyst formation and a decrease in the proportion of trophectoderm cells. Ectopic CEBPa expression in embryonic stem cells suffices to induce trophectoderm-like cells by altering the accessibility of gene regulatory elements (GREs), leading to the activation of TE-specific genes and silencing of ESC-specific genes. A cohort of trophectoderm GREs become accessible in 4- and 8-cell embryos, coinciding with CEBPa expression and binding to these enhancer regions. CEBPa may thus equip totipotent blastomeres of 4- to 8-cell embryos with future trophectoderm competence, setting the stage for the earliest developmental bifurcation.
Keywords
Trofoectodermo, CEBPa, Factores de transcripción, Especificación de linaje, Desarrollo embrionario preimplantacional, Trophectoderm, Transcription factors, Lineage specification, Preimplantation embryo development
Subjects
576 - Cellular and subcellular biology. Cytology
Publisher
Universitat Pompeu Fabra
