Evidence map›Paper›PMID 41533515›Full record

ArticleCell reports2026

Differentiation in the human urothelia is defined by distinct alternative polyadenylation.

Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Ninh B LeDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Surbhi SonaDepartment of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
Briana SantoDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yi ZhangDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rosie OuDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
R Allen SchweickartDepartment of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH, USA.
Veena KochatDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; MDACC Epigenomics Therapy Initiative (METI), Houston, TX, USA.
William I PadronDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; MDACC Epigenomics Therapy Initiative (METI), Houston, TX, USA.
Kunal RaiDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; MDACC Epigenomics Therapy Initiative (METI), Houston, TX, USA.
Shih-Han LeeDepartment of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joo Mi YiDepartment of Microbiology and Immunology, Inje University College of Medicine, Busan, South Korea.
Oliver WesselyDepartment of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH, USA.
Byron H LeeDepartment of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: bhlee@mdanderson.org.
Angela H TingDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ahting@mdanderson.org.

Funding

High resolution transcriptome and gene regulatory mapping of human ureter and bladder across the lifespanU01DK131383 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI LEE, BYRON H, TING, ANGELA H · 2021 to 2025
$2.4M
Understanding the full spectrum of epigenetic vulnerability in cancer through the delineation of DNA methylation function in gene 3' endR01CA230033 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI TING, ANGELA H · 2019 to 2023
$2.0M
NCI NIH HHS R01 CA230033NIDDK NIH HHS U01 DK131383
6 · The paper itself

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.

Indexed as

Cell DifferentiationPolyadenylationUrothelium3' Untranslated RegionsHumansRNA, MessengerTranscriptome3' Untranslated RegionsRNA, Messengeralternative cleavage and polyadenylationAPACP: GenomicsCP: Molecular biologyhuman urotheliummRNA isoformpoly(A)polyadenylationsingle-cell RNA sequencingsingle-cell spatial gene expressionurothelial differentiation

Identifiers

PMID41533515
PMCPMC12937501

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.