Differentiation in the Human Urothelia Is Defined by Distinct Alternative Polyadenylation

Authors

Ninh B Le
Surbhi Sona
Briana Santo
Yi Zhang
Rosie Ou
R Allen Schweickart
Veena Kochat
William I Padron
Kunal Rai
Shih-Han Lee
Joo Mi Yi
Oliver Wessely
Byron H Lee
Angela H Ting

Language

English

Publication Date

1-27-2026

Journal

Cell Reports

DOI

10.1016/j.celrep.2025.116839

PMID

41533515

PMCID

PMC12937501

PubMedCentral® Posted Date

2-27-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated gene- and context-dependent control of protein expression by alternative 3' untranslated regions (3' UTRs), consistent with in situ protein patterns. Conserved motifs in APA-regulated 3' UTRs, including transcription factor binding sites and Alu elements, suggest mechanisms for polyadenylation site selection. Our study establishes APA as a key contributor to transcriptomic complexity in the human urothelium.

Keywords

Humans, Polyadenylation, 3' Untranslated Regions, Urothelium, Cell Differentiation, RNA, Messenger, Transcriptome

Published Open-Access

yes

Recommended Citation

Le, Ninh B; Sona, Surbhi; Santo, Briana; et al., "Differentiation in the Human Urothelia Is Defined by Distinct Alternative Polyadenylation" (2026). Faculty, Staff and Student Publications. 6075.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6075