*Result*: Analysis of Transcriptome and Differentially Expressed Genes in Chicken Primordial Germ Cells.

*Simple Summary: Successful genome editing using primordial germ cells requires a detailed understanding of their functioning during embryonic development. In this study, we performed, for the first time, a comparative transcriptome analysis between chicken primordial germ cells and adult liver cells. We identified a total of 1909 differentially expressed genes involved in intracellular metabolism and protein biosynthesis, including transcription, translation, and post-translational protein modifications. This expression signature is consistent with the highly active and undifferentiated state of primordial germ cells during early embryogenesis. The findings provide a valuable resource for understanding gene activity within avian germ cells and establish a foundational transcriptomic signature for primordial germ cells. This knowledge could potentially serve as an important tool for maintaining the genetic biodiversity of unique, small, and endangered chicken populations and breeds. Achieving successful primordial germ cell (PGC)-based genome editing requires a deep understanding of their molecular identity. For the first time, a comparative transcriptomic analysis of chicken PGCs and adult liver cells to define their specific gene expression signature was performed. PGCs were isolated from Rhode Island Red chicken embryos, cultured, and subjected to RNA sequencing alongside liver tissue. Differential expression analysis with Benjamini–Hochberg correction identified 1909 differentially expressed genes (DEGs). Functional annotation revealed that PGCs possess a unique transcriptional landscape, characterized not only by enhanced proliferation and metabolic activity but also by a profound molecular convergence with neural crest cells. This is evidenced by the upregulation of gene modules governing long-range migration, neuronal signaling, and specialized "neuro-lipid" metabolism (e.g., sphingolipid and plasmalogen pathways). Additionally, we identified unannotated transcripts linked to immune pathways and ciliary signaling. Our study expands the functional annotation of avian PGCs and reveals an unexpected evolutionary recruitment of conserved morphogenetic programs, providing a refined molecular foundation for advanced germline editing technologies. [ABSTRACT FROM AUTHOR]*