Pluripotency revisited: sequential roles of Oct4 during mouse development

Línea de investigación

Functional Genomics.

Descripción

Pluripotency is the property of stem cells by which they can give raise to all different cell types of the adult body. This state is under the regulation of a handful of transcription factors, most notably OCT4, SOX2 and NANOG. These factors are expressed during preimplantación stages of mammalian development, when pluripotent stem cells are present in vivo. However, this is a transient state and the exit from pluripotency gives way to the orderly appearance of different lineages and cell types.

OCT4 is critical for pluripotency, but most surprisingly, it is expressed after implantation in a plethora of cell types and structures, even after pluripotency per se has already gone extinct in the mammalian embryo. This suggests further roles for this master pluripotency factor in later developmental stages. By using two complementary mouse models (a doxycycline-inducible Oct4-gain-of-function model and tamoxifen-inducible Oct4-loss-of-function one), and embryonic stem cells derived from those, we plan to unveil new roles for this transcription factor. Preliminary data already points to it having unexpected functions, such as repressing germ cell specification (clashing with all previously known data linking OCT4 to primordial germ cells) or regulating cellular metabolic states through the mTOR pathway.

The student to join our group will work within this research line, for which he will learn essential skills such us early post-implantation embryo dissection, embryo culture, embryonic stem cell culture and differentiation, transcriptomic and proteomic analysis, or genome editing, to name a few. The results from this project will open up new lines of research dealing with the fundamental question of how and when a cell decides to leave pluripotency in the living embryo, and progress along a lineage-specific developmental pathway.

The ideal candidate would have a keen interest in understanding how the embryo develops, together with a great deal of curiosity. Knowledge in tissue culture, animal handling and basic computer skills are a plus, although not strictly required. Fluency in English and a good academic record are also desirable.

Contacto

Miguel Manzanares.

Correo electrónico: mmanzanares@cbm.csic.es.