Single-Cell Transcriptomic Map of the Human and Mouse Bladders

Significance Statement Previous studies of bladder cell classification mostly relied on the cell’s morphology, location, electrophysiology, and function. However, it is difficult to classify bladder cells accurately and comprehensively using these methods. The authors created a single-cell transcriptomic map of human bladder cells using single-cell RNA sequencing. They also created a more detailed single-cell sequencing RNA map of the mouse bladder than what was previously available. Using these tools, the authors compare the similarities and differences between human and mouse bladder cells and found many cell types that are highly similar across the two. Additionally, the authors discovered two new types of human bladder cells. One may play a role in allergic reactions and nerve conduction, whereas the other may play a role in bladder emptying. The results may assist scientists studying the relationship between bladder cell types and diseases. Background Having a comprehensive map of the cellular anatomy of the normal human bladder is vital to understanding the cellular origins of benign bladder disease and bladder cancer. Methods We used single-cell RNA sequencing (scRNA-seq) of 12,423 cells from healthy human bladder tissue samples taken from patients with bladder cancer and 12,884 cells from mouse bladders to classify bladder cell types and their underlying functions. Results We created a single-cell transcriptomic map of human and mouse bladders, including 16 clusters of human bladder cells and 15 clusters of mouse bladder cells. The homology and heterogeneity of human and mouse bladder cell types were compared and both conservative and heterogeneous aspects of human and mouse bladder evolution were identified. We also discovered two novel types of human bladder cells. One type is ADRA2A + and HRH2 + interstitial cells which may be associated with nerve conduction and allergic reactions. The other type is TNNT1 + epithelial cells that may be involved with bladder emptying. We verify these TNNT1 + epithelial cells also occur in rat and mouse bladders. Conclusions This transcriptomic map provides a resource for studying bladder cell types, specific cell markers, signaling receptors, and genes that will help us to learn more about the relationship between bladder cell types and diseases.