Gene expression and immune cell heterogeneity in inbred Amur tiger

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 individual, a comprehensive understanding can be gained regarding 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. Here, for the first time, a detailed single-cell sequencing atlas of peripheral blood samples obtained from Amur tigers is presented, delineating eight distinct cell types. Our study demonstrates that the inbred tiger exhibits a relatively lower proportion of lymphocytes and cDC2 cells, along with reduced intercellular interactions. We also observed elevated activity in several signaling pathways (e.g., TGFb, APRIL, BAG, GRN, VISFATIN) that have been linked to inflammation and cancer in other species. The WGCNA analysis analysis further suggested a candidate regulatory network in inbred tiger, with the cancer-associated gene YTHDC2 emerging as a hub gene. Together, our exploratory study offers preliminary insights into the immune heterogeneity in inbred Amur tigers and can potentially guide future studies aimed at enabling timely health interventions for this endangered species.