The Morphological, Behavioral, and Transcriptomic Life Cycle of Anthrobots

Fascinating aspects of morphogenetic and behavioral plasticity of living material are revealed by novel constructs that self-construct from genetically wild-type cells. Anthrobots arise from cultured adult human airway epithelial cells, developing, becoming self-motile, and acquiring neural repair capabilities without exogenous genetic circuits or inorganic scaffolds. Progress in bioengineering and regenerative medicine depends on developing a predictive understanding of collective cell behavior in novel circumstances. Toward that end, here a number of life cycle properties of Anthrobots, including their morphogenesis, maturation, and demise, are quantitatively characterized. A self-healing capacity and a remarkable reduction of epigenetic age upon morphogenesis are uncovered. Transcriptomic analysis reveals that assembling into Anthrobots drives a massive remodeling of gene expression relative to their cellular source, including several embryonic patterning genes, and a shift toward more evolutionarily ancient gene expression. These data reveal new aspects of engineered multicellular configurations, in which wild-type adult human cells self-assemble into an active living construct with its own distinct transcriptome, morphogenesis, and life history.