CELLIDRECUT
Financiado
Cell identity reprogramming via ONECUT factors
Neuronal loss is at the core of cognitive and functional failures of both acute brain injuries and neurodegenerative diseases. Direct neuronal reprogramming of local glial cells is emerging as a promising approach for restorative...
Neuronal loss is at the core of cognitive and functional failures of both acute brain injuries and neurodegenerative diseases. Direct neuronal reprogramming of local glial cells is emerging as a promising approach for restorative brain therapy. However, in order to use direct glia-to-neuron reprogramming for the treatment of neuronal loss we still need to address a number of challenges, namely reliable and long-term conversion into the desired neuron subtype. In this proposal we aim to generate specific neuronal subtypes using novel fate determinants in glia-to-neuron reprogramming, and to provide a detailed molecular analysis of the newly generated neurons over time. Our data indicate that ONECUT factors may represent excellent novel candidates for astrocyte reprogramming into neuronal fates. To address this possibility, in this proposal we will focus on the thalamocortical system, which represents the main input to the neocortex and it is essential to cortical processing. We hypothesize that the innovative combination of nuclei specific thalamic factors with ONECUT factors could reveal new avenues for the direct reprogramming of astrocytes into thalamic neurons of specific sensory modalities and may inform future strategies for brain repair. Here, we have unique expertise and molecular tools at hand that will allow us to reprogram astrocytes into specific neuron types in vitro and in vivo. Moreover, as our ultimate goal is to reprogram astrocytes to recover neuronal loss, we will test whether astrocytes from a sensory deprived thalamus can be reprogrammed. By using state-of-the-art techniques such as 3D light-sheet microscopy, calcium imaging and transcriptomic analysis, we will determine the fidelity and functionality of the newly generated neurons. This approach will offer us unparalleled advantages for the discovery of novel reprogramming combinations and address important questions about reliable and long-term conversion into the desired neuron type.
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Duración del proyecto: 31 meses
Fecha Inicio: 2022-06-27
Fecha Fin: 2025-01-31
Fecha Fin: 2025-01-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-06-27
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2021-PF-01-01:
MSCA Postdoctoral Fellowships 2021
Cerrada
hace 3 años
Presupuesto
El presupuesto total del proyecto asciende a
181K€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA...
Investigaciones agrarias
Perfil tecnológico
TRL
2-3
716M
Perfil tecnológico
TRL
2-3
716M