2025/11/14 by Eva Hamrud, Jacob Leese, Alexandre P Thiery +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #Single-cell and spatial transcriptomics #Pluripotent Stem Cells Research
paper · doi:10.1242/dev.204943
openalex created_date 2025/11/14 · openalex publication_date 2025/11/14 · openalex updated_date 2026/08/01
During development, dynamic changes in gene expression and chromatin architecture drive the transition from progenitors to specialised cell types. Here, we use single cell ATAC sequencing (scATAC-seq) to investigate changes in chromatin accessibility as chick neural plate border cells segregate into neural, neural crest and placode cells. We developed a Nextflow pipeline, 'single cell Advanced Chromatin Exploration', which integrates scATAC-seq and scRNA-seq data to identify cell-state-specific accessibility profiles and groups of chromatin regions with coordinated dynamic behaviour, termed accessibility modules. We find that neural plate border and adjacent cells are characterised by broadly open chromatin, reflecting their broad potential to generate any ectodermal derivative. As development proceeds, cell-type-specific chromatin signatures are established. Inferring an enhancer-centric gene regulatory network, we predict Foxk2 as new regulator for placode specification and verify this prediction experimentally. Foxk2 target enhancers are open in placodal cells, but not any other ectodermal cells. This finding suggests that, on a regulatory level, cells can use different strategies to control fate choice: differential accessibility of enhancers and broad accessibility controlled by differentially expressed transcription factors.