SC-EpiCode
Financiado
Decoding the Epigenomic Regulatory Code by the Use of Single Cell Technologies
Chromatin regulators adjust genome functions by modifying chromatin states. Comprehensive characterization of chromatin states, associations of chromatin regulators, and expression profiles is crucial for investigating: 1.Cellular...
Chromatin regulators adjust genome functions by modifying chromatin states. Comprehensive characterization of chromatin states, associations of chromatin regulators, and expression profiles is crucial for investigating: 1.Cellular differentiation triggers. 2.The nature of the underlying chromatin regulatory mechanisms. 3.The effect of cellular heterogeneity, and 4. How chromatin affects mRNA expression. Mapping chromatin states by sequencing immunoprecipitated chromatin (ChIP-seq) provides an extraordinary resource for studying cellular states. However, a major shortcoming is that the profiles reflect a composite average over the studied cell population, concealing important information about the underlying subpopulations. To address this hurdle, I pioneered Drop-Seq, a novel drop based microfluidic technology for single cell ChIP-seq and RNA-seq. Applying the technique to thousands of embryonic stem (ES) cells, we identified a spectrum of sub-populations defined by differences in chromatin signatures of pluripotency and differentiation priming. However, despite initial progress, the extent and significance of chromatin-state heterogeneity and its relationship with mRNA expression remain largely uncharted. The central aim of this proposal is to develop a novel framework to systematically characterize cell-to-cell variability at the epigenomic level. Our approach will include the development of technology enabling ChIP-seq and RNA-seq on the same cell. We will also exploit drop-based microfluidics to develop a robust CRISPR/Cas9-based approach to assess single and multiple perturbations. Finally, we will apply these innovative technologies to questions about cellular heterogeneity and epigenomic regulation during early differentiation of ES cells. This proposal will reveal the function and interplay between chromatin regulators, histone marks and transcription events, and shed light on the underlying regulation leading to cell fate decisions.
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Duración del proyecto: 66 meses
Fecha Inicio: 2017-09-26
Fecha Fin: 2023-03-31
Fecha Fin: 2023-03-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2023-03-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2016-STG:
ERC Starting Grant
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
THE HEBREW UNIVERSITY OF JERUSALEM
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
260.16K€ |
Participante