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Transcription Factor-mediated Neuronal Cell Fate Programming in Human Stem Cells

Objective

The discovery of pluripotent stem cells has expanded the working modes in biology towards the reverse engineering of specific cell types. Unlike studying developmental phenomena in vivo, we are now theoretically able to mimic some of these processes in a dish. The use of human induced pluripotent stem (iPS) cells facilitates studying the genesis of human cell types in an ethically approved setting. However, exploiting the full potency of stem cells is only possible with very few differentiated cell types. In particular, the generation of neurons is in its infancy: of the many neuronal types present in the brain, only a few types have been generated in vitro. So far, neuronal differentiation protocols are multifaceted and tailored to individual cell types. The molecular events that occur during reprogramming remain enigmatic. Hence, we cannot confer these protocols easily on producing different neurons of interest. Therefore, we plan to induce transcription factors as differentiation control buttons in human iPS cells in order to explore in vitro neurogenesis systematically. First, we will apply a human transcription factor library to conditional fluorescent iPS reporter lines, facilitating high-throughput isolation and analysis of induced neurons. Second, the underlying gene regulatory networks will be revealed using RNA-sequencing over the entire differentiation period to identify the biological rules of in vitro neuronal differentiation. We will combine these in-depth transcriptomic analyses with morphological, anatomical, and functional characterizations. Finally, based on our discoveries, we will engineer human photoreceptors that can be applied to cell transplantation experiments in retinal degeneration diseases. Conceptually, our approach paves the way for targeted “forward” programming of human iPS cells to neurons.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2015-STG

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Host institution

TECHNISCHE UNIVERSITAET DRESDEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 482 500,00
Address
HELMHOLTZSTRASSE 10
01069 DRESDEN
Germany

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Region
Sachsen Dresden Dresden, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 482 500,00

Beneficiaries (2)

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