ABSTRACT: Inbreeding leads to a reduction in genetic diversity and an elevated likelihood of expressing recessive defective genes, which adversely affect the development of the immune system and render individuals and populations more susceptible to carcinogenic factors, consequently heightening the risk of cancer. Through investigating the function and extent of immune cell interaction in peripheral blood mononuclear cells (PBMCs) of inbred individuals, one can gain a comprehensive understanding of the impact of inbreeding on various aspects of the immune system, including diversity, self-tolerance, immune responsiveness, susceptibility to diseases, and other related areas. Currently, the wild Amur tiger population in China exhibits a moderate degree of inbreeding, with a probability exceeding 90% that it will be deemed extinct within the forthcoming century. However, the impact of inbreeding on the immune system remains ambiguous, presenting numerous challenges for the development and implementation of conservation strategies. The present study presents, for the first time, a detailed single-cell sequencing atlas of peripheral blood samples obtained from Amur tigers, delineating eight distinct cell types. Research findings show that inbred individuals have a lower percentage of lymphocytes and cDC2 cells, as well as diminished intercellular interactions compared to non-inbred individuals. Meanwhile, inbred individuals exhibited significantly increased expression of signaling pathways such as TGFb, APRIL, BAG, GRN, and VISFATIN, which are closely associated with inflammation and cancer. Moreover, the WGCNA analysis unveiled the core gene regulatory network specific to inbred individuals, highlighting a robust correlation between inbreeding and the cancer-related gene YTHDC2. Our study presents a comprehensive analysis of PBMC characteristics in the Amur tigers and reveals the possibility of increased susceptibility to cancer and inflammation associated with inbreeding. These findings provide novel insights into the immune heterogeneity in the inbred Amur tiger and furnish valuable data supporting timely treatment for affected individuals.
