Systems Level Analysis of ES Cell Differentiation

Development of higher eukaryotic organisms proceeds through a series of cell fate transitions, typically accompanied by a decline in developmental potency. Research in recent years has contributed to a substantial understanding of the molecular underpinnings of pluripotency. However, the mechanisms that compute cues from the cellular environment to elicit a regulated and exact cell fate choice are currently unknown. As a consequence, primary lineage decisions from mammalian pluripotent cells cannot be properly controlled experimentally. An interdisciplinary approach between the stem cell researchers from the group of Martin Leeb (MFPL, Vienna) and computational biologists from the group of Andreas Beyer (University of Cologne) will focus on filling this gap in knowledge. In a first step will systematically identify genes required for the differentiation of embryonic stem cells. We will then use this information in order to investigate the molecular mode of action of those genes, their downstream targets and if and how they interact with each other. These experiments will utilize state of the art genome engineering technology to generate mutant ES cells efficiently and at large scale. This will be followed by detailed transcriptional profiling using next generation sequencing. Together our project will contribute to a deeper understanding of the mechanisms that drive and maintain cell identity.

Development of higher eukaryotic organisms proceeds through a series of cell fate transitions, typically accompanied by a decline in developmental potency. Research in recent years has contributed to a substantial understanding of the molecular underpinnings of pluripotency. However, the mechanisms that compute cues from the cellular environment to elicit a regulated and exact cell fate choice are currently unknown. As a consequence, primary lineage decisions from mammalian pluripotent cells cannot be properly controlled experimentally. An interdisciplinary approach between the stem cell researchers from the group of Martin Leeb (MFPL, Vienna) and computational biologists from the group of Andreas Beyer (University of Cologne) will focus on filling this gap in knowledge. In a first step will systematically identify genes required for the differentiation of embryonic stem cells. We will then use this in formation in order to investigate the molecular mode of action of those genes, their downstream targets and if and how they interact with each other. These experiments will utilize state of the art genome engineering technology to generate mutant ES cells efficiently and at large scale. This will be followed by detailed transcriptional profiling using next generation sequencing. Together our project will contribute to a deeper understanding of the mechanisms that drive and maintain cell identity.