Reprogramming of cellular signaling associated with diseases involves a concerted effort on the parts of transcriptional programs, chromatin dynamics, pathway activities, and cellular interactions. This work established a method of using single-cell multi-omics to define diverse cell states relevant to diseases and the dynamic signaling reprograming. After quality control, a total of 68,421 single cells/nuclei profiles were used, including 35,876 disease-related cells and 32,545 control-related cells/nuclei. Weighted k-nearest neighbor integration revealed 17 clusters of cells, and the disease-enriched abnormal cells grew from 0.052 ± 0.014 in controls to 0.241 ± 0.031 in diseases, resulting in an enrichment of +1.42 ± 0.18*. In addition, intermediate cell states were enriched significantly, reaching an enrichment of +0.77 ± 0.12*. Pseudotime analysis showed that the pseudotime value in disease cells was 0.67 ± 0.12*, higher than the control group, which was 0.24 ± 0.09*. The signaling that showed the most significant change was inflammatory signaling (a trajectory coefficient of +0.86 ± 0.10*), followed by hypoxia response (+0.69 ± 0.08*) and stress response (+0.74 ± 0.09*). The multi-omics analysis also found 1,284 up-regulated genes, 18,742 disease-enriched chromatin peaks, and 4,216 peak-to-gene connections.
Research Article
Open Access