Single-cell RNA sequencing revealed the roles of macromolecule epidermal growth factor receptor (EGFR) in the hybrid sterility of hermaphroditic Argopecten scallops.

The macromolecule epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that belongs to the protein kinase superfamily, which plays versatile functions in cell proliferation, development and fertility regulation. Almost all F hybrids obtained from the hermaphroditic bay scallops and Peruvian scallops exhibit infertility, and the genetic mechanism remains unclear. In this study, the comprehensive scRNA-seq was first conducted in the gonads of hybrid scallops, deducing the developmental sequence of germ cells and identifying the critical regulators in hybrid sterility: epidermal growth factor receptor. During the development from oogenesis phase germ cells to oocytes, the expression of the EGFR gene gradually decreased in sterile hybrids but increased in fertile hybrids. The significantly lower EGFR expression and ATP content, but higher ROS production rate was detected in the gonad of sterile hybrids than that in fertile hybrids, which might cause slow development of oocytes, stagnation of cell cycle, insufficient energy supply, high level of apoptosis and final sterility. Specific knock-down of EGFR gene led to decreased ATP content, increased ROS production rate, and inhibited oocyte maturation and gonadal development. These findings provide new insights into the roles of EGFR in hybrid infertility of bivalves and the healthy development of scallop breeding.