Innovating Works

LINMOS

Financiado
Lineage tracing of the human brain
Organisms develop through cell divisions generating clones that progressively organize to form different tissues. This process can be visualized as a cell phylogeny by lineage tracing. In order to track cell lineages, each cell di... Organisms develop through cell divisions generating clones that progressively organize to form different tissues. This process can be visualized as a cell phylogeny by lineage tracing. In order to track cell lineages, each cell division has to be permanently and uniquely marked. In model systems, this is done by genome editing. In humans this is not applicable, which has historically made impossible to accurately study cell phylogenies. Very recently, however, studies showed that human tissues contain a set of natural markers in the form of somatic DNA variants that permanently and cumulatively label every cell division during development. My work showed that somatic variants are reliable at tracking cell lineages directly in human tissues. Human brain development has historically been difficult to address since human-brain-specific features are hardly recapitulated in any existing model. My project now builds on the use of somatic variants to reveal the cellular processes that form the brain starting from available human material. Somatic variants will be identified at unprecedent sensitivity in a large set of human foetal tissues, including multiple different brain regions. In work package (WP)1, I will identify and study the lineage segregation steps defining the brain phylogeny starting from the zygote. Mathematical modelling will elucidate mechanisms of clone dynamics. In WP2, I will focus on the cerebral cortex and reconstruct cell phylogenies of neural progenitors and the distribution of cortical clones. Furthermore, I will compare normal versus overgrowth cortical malformation brains, where cell proliferation and migration are altered. In WP3, I will develop new strategies to simultaneously assess cell phylogenies and cell-type specification by identifying somatic variants in multi-omics data. This project will reveal the unfolding of the cellular lineages building the human brain, while providing a methodology that is applicable to any tissue and pathology. ver más
31/05/2029
INSERM
2M€
Duración del proyecto: 62 meses Fecha Inicio: 2024-03-08
Fecha Fin: 2029-05-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-03-08
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2023-STG: ERC STARTING GRANTS
Cerrada hace 2 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5