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How Environmental Signals Shape Epigenetic Barriers in Establishing and Reprogramming Brain Cell Fate

Subject Area Cell Biology
General Genetics and Functional Genome Biology
Term since 2025
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 563396883
 
Recent advancements in genome-wide and single-cell methodologies have highlighted extensive epigenomic variation across the many important cell types in the brain. Despite this progress, the specific chromatin modifications that are critically relevant to distinct cellular lineages remain poorly understood. This knowledge gap primarily stems from the limited availability of methods capable of concurrently manipulating multiple chromatin marks within well-characterized models of cell fate transitions in the mammalian brain. Here, we will apply scATAC-seq and RRBS to characterize epigenomic differences between four different astrocyte states, two susceptible to neuronal induction, two not; two derived from mouse brains, the other two differentiated from human iPSCs. Next, we will apply a novel strategy allowing efficient manipulation of chromatin accessibility and DNA de-methylation of multiple chromatin differences (dRNPs) in well-established models of astrocyte to neuron reprogramming. Following this experimental strategy will allow elucidating the role of chromatin dynamics for cell identity barriers and advance our understanding of brain cell lineage specification during neurodevelopmental processes.
DFG Programme Priority Programmes
 
 

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