Stellate stromal cells may underpin the body’s massive pattern-memory capacity
June 22
Recent in vivo studies have overturned the long-held view that stromal stellate cells, which constitute at least half of the cells in many developing and regenerating tissues, are merely passive scaffolds. Nevertheless, a mechanistic picture of how instructive epithelia and supportive stroma cooperate to guide large-scale pattern formation is still lacking. To bridge this gap, we present a theory of epithelium–stellate cell networks for morphogenetic memory processing, formulated within a Dense Morphogenetic Memory framework. Our analysis indicates that stellate cells are natural biological hardware for implementing such networks. Stellate cells dramatically enhance the pattern-memory capacity of the tissue. This improvement arises from storing positional information within the meshwork of stellate cell processes rather than solely in epithelial gap-junction weights, as traditionally assumed. Process-to-process signaling is expected to occur in vivo and may account for the remarkable reliability of complex regenerative outcomes.
Stellate stromal cells, the most abundant cell type in many regenerative fields, are emerging as fundamental regulators of pattern memory. Despite nearly every epithelial junction in the limb bud or planarian blastema being ensheathed by a stellate process, no current theory explains how epithelia, junctions, and stellate cells might jointly sustain pattern information. We demonstrate that key aspects of stellate morphology and physiology naturally yield a dynamic, high-capacity associative morphogenetic system. The epithelium–stellate networks produced by our framework are closely related to popular machine-learning architectures known as Dense Associative Memories. By tuning the connectivity motif, the model spans a family of memory networks that encompasses both a Dense Associative Memory and a Transformer as limiting cases. In previously described biological implementations, the ratio of stored patterns to epithelial cells remains fixed as tissue size increases. Our work reveals that epithelium–stellate networks obey a superior scaling law, surpassing known biological Dense Morphogenetic Memories. The model therefore raises an exciting and previously overlooked possibility: developmental blueprints could be archived, at least in part, within the interconnected web of stellate processes rather than exclusively in the conductance states of epithelial gap junctions.