Innovating Works

EmbryoMethFunc

Financiado
Cell Type Specific DNA Methylation Changes During Mammalian Development Beyond...
DNA methylation is essential for normal mammalian development. While seminal work has provided tremendous insight into the dynamic regulation of DNA methylation throughout embryogenesis, comprehensive understanding of how cell-spe... DNA methylation is essential for normal mammalian development. While seminal work has provided tremendous insight into the dynamic regulation of DNA methylation throughout embryogenesis, comprehensive understanding of how cell-specific methylation programs are established and maintained, and how they are involved in defining cell states in vivo through regulation of target genes, remains a formidable task. Revolutionary technologies now offer unprecedented opportunities for understanding the function of DNA methylation in specifying, memorizing and modulating embryonic programs. These powerful tools motivate further development of novel experimental systems, to integrate single-cell monitoring with flexible engineering of markers, reporters and perturbations. This will make it possible to precisely target key rare embryonic cell populations for in-depth analysis. Here, combining cutting-edge methods for single cell mapping of DNA methylation and gene expression, and by developing a novel approach for inferring spatial information from single cell genomic data, we propose to comprehensively chart the post-implantation embryo, at unprecedented resolution. To move to functional studies, we will implement our recently established reporter system that enables monitoring and isolation of cells based on endogenous locus-specific changes in DNA methylation. Together with site-specific methylation editing tools, mouse genetics, and in vitro differentiation of pluripotent stem cells, we will study the developmental potential of rare epiblast cells that we identified that exhibit lower-than-expected genome-wide methylation levels. We will further study the effects of cell-specific methylation changes at an imprinted control region on gene dosage by genetic and epigenetic perturbation, during mouse development. Our combined approach will open new avenues for elucidating the contribution of cell-specific DNA methylation changes to cell-state and function following implantation ver más
30/09/2024
WEIZMANN
2M€
Duración del proyecto: 60 meses Fecha Inicio: 2019-09-26
Fecha Fin: 2024-09-30

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2024-09-30
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2019-STG: ERC Starting Grant
Cerrada hace 6 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5