BMI Distinguished Seminar // Igor Adameyko: Clonal analysis at single cell level helps to understand neural crest development

Understanding embryonic development requires a detailed grasp of clonal fate biasing and spatial regulation within tissues. Here I will present an integrated approach to analyze cell lineages and transcriptional states in mammalian embryos from neurulation to mid-gestation. Utilizing high-throughput single-cell clonal tracing and unsupervised machine learning, we mapped continuous spectra of clonal fate bias, uncovering spatial and temporal control over cell lineage decisions. Key findings revealed that patterns of clonal variation align with gene programs driving skeletal and neurogenic differentiation. Employing the novel "clone2vec" algorithm, inspired by word embeddings, we captured clonal fates in a latent space, permitting robust dropout resistance and analysis of heterogeneity within mesodermal and ectodermal derivatives. Additionally, mosaic perturbations of signaling receptors, such as those in the Hedgehog pathway, created unique cell type assemblages in vivo, suggesting applications in tissue engineering and disease modeling