A silkworm model reveals coordinated cellular communities and conserved Hippo regulation in silk production

Silk production, a spectacular evolutionary innovation shared by approximately 143,000 arthropod species, is underpinned by genetic and cellular programs that remain incompletely resolved. Although a cellular atlas exists for the silkworm (Bombyx) silk gland (SG)—the premier model for this trait—the coordinated cellular dynamics and transcriptional logic that underlie its remarkable efficiency are unsolved. Here, we bridge this gap by an integrative meta-analysis that leverages single-cell deconvolution and high-dimensional weighted gene coexpression network analysis (hdWGCNA). Applied to existing atlases, public data, and de novo transcriptomes, this computational strategy enabled the identification of key cell subpopulations and the reconstruction of a high-resolution, global coexpression network orchestrating silk production. This network nominated the Hippo signaling pathway as a top regulatory hub. Functionally, conditional overexpression and knockout of its core effector, Yorkie (Yki), demonstrated that Yki is causal for SG development and silk protein synthesis. Further deconvolution of Yki-mutant transcriptomes confirmed the substantial impact of Hippo–Yki signaling on the cellular hierarchical framework of the SG. Our work not only deciphers a key regulatory axis controlling a classic biological trait but also provides an integrative computationally driven experimental framework, establishing a paradigm for obtaining mechanistic insights from complex omics landscapes.