# Single-Cell Deconvolution Reveals Phenotype-Associated Cellular States in the Silk Glands of Bombyx mori and Its Wild Ancestor

## TL;DR

This study shows how domestication changed the cellular states in silkworms to improve silk production, using single-cell analysis to compare domestic and wild silkworms.

## Contribution

The study introduces a cellular framework to understand how domestication reshaped silk glands for optimized silk production.

## Key findings

- Domestic silkworms have a 'pro-synthesis' cellular state with activated silk protein genes and metabolism.
- Wild silkworms maintain a 'protective–adaptive' state focused on stress response and xenobiotic metabolism.
- Pseudotime analysis identified key gene expression changes linked to high silk yield during domestication.

## Abstract

This study investigated how domestication altered silk production by comparing the cellular states in silk glands of domestic silkworm and its wild ancestor at single-cell resolution. We identified a “pro-synthesis” cellular state in domestic silkworms, characterized by activated silk protein genes and enhanced metabolism, whereas wild silkworm cells maintained a “protective–adaptive” state geared toward stress response. Trajectory analysis revealed key genetic switches associated with high silk yield. Our results demonstrate that domestication reshaped the silk gland cellular landscape toward optimized production. This work provides a new cellular framework for understanding the evolution of complex traits under selection, with implications for agriculture and functional biology.

Silk production is a classic example of a domestication trait, yet the cell-type-specific driver of its enhancement in the silkworm Bombyx mori remains unresolved. To address this, we integrated extensive bulk RNA-seq data with a single-nucleus RNA-seq atlas of silk glands (SGs) from domestic B. mori and wild B. mandarina for deconvolution analysis. This identified phenotype-associated cell subpopulations (Scissor+ and Scissor− cells) that enrich in B. mori and B. mandarina, respectively. Transcriptomic characterization revealed that B. mori SG cells exhibit a pervasive “pro-synthesis” transcriptional state, with concerted upregulation of silk protein genes and metabolic pathways. Conversely, B. mandarina cells maintained a “protective–adaptive” state, enriched for stress response and xenobiotic metabolism genes. Pseudotime analysis further delineated the cell state transitions, pinpointing key dynamic gene expression linked to high silk yield. Our findings demonstrate that domestication reshaped the silk gland cellular landscape, promoting a systemic shift toward a synthesis-optimized cell state. This study offers a new framework at the cellular level to elucidate the evolution of complex traits under selection.