Figure 14. Patients with chronic gut dysmotility show significant shifts in their normal proportions of the two neuronal lineages.

(a) ProjectR-based projection of bulkRNAseq data from intestinal specimens of patients with normal motility and patients with obstructive defecation (OD), a chronic condition of intestinal dysmotility, into the 50 different NMF patterns learnt earlier, shows that the MEN-specific NMF patterns 32 and 41 were significantly upregulated in bulk-RNAseq of OD patients compared to controls. Data represent mean ± S.E.M. One-way ANOVA. Data mined from raw data generated by Kim et al., 2019 (b) OD patients show a significant decrease in the expression of important NENs-associated genes such as Ret, Gdnf, Snap-25, Nos1, Klhl1, and Chat, while showing a significant increase in the expression of important MENs-specific genes such as Clic3, Upk3a, Cdh3, Slpi, and Slc17a9. Data taken from Kim et al., 2019.

Figure 14—figure supplement 1. Projection of the bulk RNA sequencing data of intestinal tissue from Control and Patients with Obstructed Defecation into our murine scRNAseq-derived NMF patterns using projectR.

Transcriptomic data from intestinal tissues of patients with normal intestinal motility and those with obstructed defecation (OD) was procured from GEO (GSE101968). Non-negative matrix factorization (NMF), as implemented in the R package NNLM (https://github.com/linxihui/NNLM; Lin and Boutros, 2020), was performed on the murine scRNAseq data using k=50 and default parameters; and cell weights for each pattern were grouped. Using projectR, the log2 expression (log2(rpkm +1)) from the human bulk RNA sequencing data from control and OD patients were projected into the murine scRNAseq-derived NMF patterns. The mean projection weights from Control and OD groups were tested for statistically significant differences using Students’ t tests.