Pseudotime Ordering Single-Cell Transcriptomic of ß Cells Pancreatic Islets in Health and Type 2 Diabetes.

ABSTRACT

ß cells are defined by the ability to produce and secret insulin. Recent studies have evaluated that human pancreatic ß cells are heterogeneous and demonstrated the transcript alterations of ß cell subpopulation in diabetes. Single-cell RNA sequence (scRNA-seq) analysis helps us to refine the cell types signatures and understand the role of the ß cells during metabolic challenges and diseases. Here, we construct the pseudotime trajectory of ß cells from publicly available scRNA-seq data in health and type 2 diabetes (T2D) based on highly dispersed and highly expressed genes using Monocle2. We identified three major states including 1) Normal branch, 2) Obesity-like branch and 3) T2D-like branch based on biomarker genes and genes that give rise to bifurcation in the trajectory. ß cell function-maintain-related genes, insulin expression-related genes, and T2D-related genes enriched in three branches, respectively. Continuous pseudotime spectrum might suggest that ß cells transition among different states. The application of pseudotime analysis is conducted to clarify the different cell states, providing novel insights into the pathology of ß cells in T2D. Supplementary Information The online version contains supplementary material is available at 10.1007/s43657-021-00024-z.