Mass cytometry and transcriptomic profiling reveal body-wide pathology induced by Loxl1 deficiency

The loss of LOXL1 expression reportedly leads to the prolapse of pelvic organs or to exfoliation syndrome glaucoma. Increasing evidence suggests that LOXL1 deficiency is associated with the pathogenesis of several other diseases. However, the characterization of the systemic functions of LOXL1 is limited by the lack of relevant investigative technologies.

To determine the functions of LOXL1, a novel method for body-wide organ transcriptome profiling, combined with single-cell mass cytometry, was developed. A body-wide organ transcriptomic (BOT) map was created by RNA-Seq of tissues from 17 organs from both Loxl1 knockout (KO) and wild-type mice.

The BOT results indicated the systemic upregulation of genes encoding proteins associated with the immune response and proliferation processes in multiple tissues of KO mice, and histological and immune staining confirmed the hyperplasia and infiltration of local immune cells in the tissues of KO mice. Furthermore, mass cytometry analysis of peripheral blood samples revealed systemic immune changes in KO mice. These findings were well correlated with results obtained from cancer databases. Patients with tumours had higher Loxl1 mutation frequencies, and patients with Loxl1-mutant tumours showed the upregulation of immune processes and cell proliferation and lower survival rates.

This study provides an effective strategy for the screening of gene functions in multiple organs and also illustrates the important biological roles of LOXL1 in the cells of multiple organs as well as in systemic immunity.