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On the molecular basis of mammalian totipotency
On the molecular basis of mammalian totipotency
The transient capacity to autonomously form and organize all of the embryonic and extra- embryonic tissues involved in the development of a complete organism is termed totipotency. In mammals, totipotency is a feature restricted to the earliest cells of the pre-implantation embryo, which harbor this unique capacity during the first 1-3 cell cycles, depending on the species. However, our understanding of the regulatory mechanisms responsible for the establishment, maintenance and termination of such a highly plastic regulatory state remains limited. Mammalian totipotency occurs concomitantly to a set of highly-intermingled biological processes such as global chromatin remodeling, an unusual set of metabolic characteristics and the de-repression of the vast majority of transposable elements, and it is unclear whether these processes act to sustain it. Following a general overview of these processes, in this dissertation I present my contributions to a body of work on an in vitro model system for mammalian totipotency, which exhibits certain molecular features of the in vivo totipotent state. Afterwards, in the second part of this thesis, I present the transcriptional analyses that I have conducted with the aim of understanding the role of transposable element transcription during pre-implantation development. Overall, this work describes a set of phenomena that arise in totipotent cells in vivo and in totipotent-like cells in vitro and explores how recapitulating certain molecular features of totipotent cells in pluripotent cells induces a totipotent-like state in vitro.
Totipotency, pluripotency, transposons, stem cells, single cell genomics
Rodriguez-Terrones, Diego
2019
English
Universitätsbibliothek der Ludwig-Maximilians-Universität München
Rodriguez-Terrones, Diego (2019): On the molecular basis of mammalian totipotency. Dissertation, LMU München: Faculty of Biology
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Abstract

The transient capacity to autonomously form and organize all of the embryonic and extra- embryonic tissues involved in the development of a complete organism is termed totipotency. In mammals, totipotency is a feature restricted to the earliest cells of the pre-implantation embryo, which harbor this unique capacity during the first 1-3 cell cycles, depending on the species. However, our understanding of the regulatory mechanisms responsible for the establishment, maintenance and termination of such a highly plastic regulatory state remains limited. Mammalian totipotency occurs concomitantly to a set of highly-intermingled biological processes such as global chromatin remodeling, an unusual set of metabolic characteristics and the de-repression of the vast majority of transposable elements, and it is unclear whether these processes act to sustain it. Following a general overview of these processes, in this dissertation I present my contributions to a body of work on an in vitro model system for mammalian totipotency, which exhibits certain molecular features of the in vivo totipotent state. Afterwards, in the second part of this thesis, I present the transcriptional analyses that I have conducted with the aim of understanding the role of transposable element transcription during pre-implantation development. Overall, this work describes a set of phenomena that arise in totipotent cells in vivo and in totipotent-like cells in vitro and explores how recapitulating certain molecular features of totipotent cells in pluripotent cells induces a totipotent-like state in vitro.