# Single-cell profiling defines the cellular landscape of the urinary bladder: a scoping review

**Authors:** Eugene Padi, Alexander Guldmann Clausen, Anastasia Buch Kjeldgaard, Mahboobeh Amoushahi, Clara Ibel Chamorro, Magdalena Fossum

PMC · DOI: 10.1186/s40001-025-03750-6 · European Journal of Medical Research · 2026-01-05

## TL;DR

This review maps the use of single-cell RNA sequencing to understand the diverse cell types in the healthy urinary bladder and identifies research gaps.

## Contribution

A comprehensive scoping review of single-cell RNA sequencing studies on bladder cell heterogeneity, highlighting novel cell types and methodological insights.

## Key findings

- Twelve studies identified various bladder cell subtypes, including urothelial, immune, and neural cells.
- A landmark study distinguished mural cells from fibroblasts, and another compared single-cell and single-nuclei RNA sequencing methods.
- Data integration and validation across modalities are essential for resolving the bladder's cellular complexity.

## Abstract

The urinary bladder contains a heterogeneous cell population. Multiple studies utilizing single-cell RNA sequencing techniques have uncovered the complex transcriptomic profile of cells in the healthy bladder.

The present study aims to map existing evidence on the use of single-cell RNA sequencing to assess cellular heterogeneity in the healthy urinary bladder and to identify gaps in the literature that could guide future research.

We searched four online databases, supplemented with manual searches, to identify relevant studies that characterized various cell types of the bladder at single-cell resolution. Studies that did not meet the predefined inclusion criteria were excluded based on a protocol drafted a priori. We included only studies published in English.

Twelve studies met the inclusion criteria, investigating various subtypes of cells: urothelial, interstitial, smooth muscle, immune, endothelial, mesothelial, and neural. A landmark study differentiating mural cells from fibroblasts was also presented. Another study compared the use of single-cell with single-nuclei RNA sequencing to assess the utility of the latter for cell identification. We further discussed the gaps and requirements necessary to implement single-cell RNA sequencing in a clinical setting.

The combined results highlight several rare and newly identified cell types in different compartments of the urinary bladder. Data integration and validation across multiple modalities are critical steps forward to resolve the cellular complexity of the urinary bladder.

The online version contains supplementary material available at 10.1186/s40001-025-03750-6.

## Full-text entities

- **Genes:** Des (desmin) [NCBI Gene 13346], Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, VIM (vimentin) [NCBI Gene 7431], Upk3b [NCBI Gene 80761], Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Cxcl13 (C-X-C motif chemokine ligand 13) [NCBI Gene 55985] {aka 4631412M08Rik, ANGIE2, Angie, BCA-1, BLC, BLR1L}, DCN (decorin) [NCBI Gene 1634] {aka CSCD, DSPG2, PG40, PGII, PGS2, SLRR1B}, Krt20 (keratin 20) [NCBI Gene 66809] {aka 9030623C06Rik, Ck-20, Ck20, K20, Krt21}, Wnt2 (wingless-type MMTV integration site family, member 2) [NCBI Gene 22413] {aka 2610510E18Rik, Int1l1, Irp, Mirp, Wnt-2, Wnt2a}, Msln (mesothelin) [NCBI Gene 56047] {aka C-ERC, MPF}, MCM2 (minichromosome maintenance complex component 2) [NCBI Gene 4171] {aka BM28, CCNL1, CDCL1, D3S3194, DFNA70, MITOTIN}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}, COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275] {aka 18A2, 42A, CAPL, FSP1, MTS1, P9KA}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Scara5 (scavenger receptor class A, member 5) [NCBI Gene 71145] {aka 4932433F15Rik, 4933425F03Rik, Tesr}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, E2f2 (E2F transcription factor 2) [NCBI Gene 242705] {aka E2F-2}, Car3 (carbonic anhydrase 3) [NCBI Gene 12350] {aka Ca3, Car-3}, Lmnb1 (lamin B1) [NCBI Gene 16906], Cyp2b10 (cytochrome P450, family 2, subfamily b, polypeptide 10) [NCBI Gene 13088] {aka Cyp2b, Cyp2b20, p16}, Slc17a7 (solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 7) [NCBI Gene 72961] {aka 2900052E22Rik, Vglut1}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Cd34 (CD34 antigen) [NCBI Gene 12490], COL3A1 (collagen type III alpha 1 chain) [NCBI Gene 1281] {aka EDS4A, EDSVASC, PMGEDSV}, PLXNA4 (plexin A4) [NCBI Gene 91584] {aka FAYV2820, PLEXA4, PLXNA4A, PLXNA4B, PRO34003}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Hes1 (hes family bHLH transcription factor 1) [NCBI Gene 15205] {aka Hry, bHLHb39}, Npy1r (neuropeptide Y receptor Y1) [NCBI Gene 18166] {aka NPY1-R, Npyr, Y1-R}, Sele (selectin, endothelial cell) [NCBI Gene 20339] {aka CD62E, E-selectin, ELAM-1, Elam, LECAM2}, Vcam1 (vascular cell adhesion molecule 1) [NCBI Gene 22329] {aka CD106, Vcam-1}, Actg2 (actin, gamma 2, smooth muscle, enteric) [NCBI Gene 11468] {aka ACTA3, Act-4, Act4, SMGA}, Tnc (tenascin C) [NCBI Gene 21923] {aka C130033P17Rik, Hxb, TN, TN-C, Ten, cytotactin}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, FOXA1 (forkhead box A1) [NCBI Gene 3169] {aka HNF3A, TCF3A}, Col1a2 (collagen, type I, alpha 2) [NCBI Gene 12843] {aka Col1a-2, Cola-2, Cola2, oim}, Upk3b (uroplakin 3B) [NCBI Gene 100647] {aka P35, PMS2L14, UpIIIb}, Prss27 (serine protease 27) [NCBI Gene 213171] {aka CAPH2, Mpn, marapsin}, CD34 (CD34 molecule) [NCBI Gene 947], Adgre1 (adhesion G protein-coupled receptor E1) [NCBI Gene 13733] {aka DD7A5-7, EGF-TM7, Emr1, F4/80, Gpf480, Ly71}, Wtip (WT1 interacting protein) [NCBI Gene 101543], Ifitm1 (interferon induced transmembrane protein 1) [NCBI Gene 68713] {aka 1110036C17Rik, DSPA2a, Mil-2, Mil2}, Jchain (immunoglobulin joining chain) [NCBI Gene 16069] {aka 9530090F24Rik, Igj, Jch}, Krt5 (keratin 5) [NCBI Gene 110308] {aka 3300001P10Rik, CK5, K5, Krt2-5, Tfip8}, HRH2 (histamine receptor H2) [NCBI Gene 3274] {aka H2R, HH2R}, Krt19 (keratin 19) [NCBI Gene 16669] {aka CK-19, EndoC, K19, Krt-1.19, Krt1-19}, Vim (vimentin) [NCBI Gene 22352], Myocd (myocardin) [NCBI Gene 214384] {aka BSAC2A, Srfcp}, Tesc (tescalcin) [NCBI Gene 57816] {aka 1010001A17Rik, 2410011K10Rik, TE-1}, Fcrl5 (Fc receptor-like 5) [NCBI Gene 329693] {aka Fcrh3, mBXMH2}, Trp63 (transformation related protein 63) [NCBI Gene 22061] {aka Ket, P51/P63, P63, P73l, Tp63, Trp53rp1}, ASPM (assembly factor for spindle microtubules) [NCBI Gene 259266] {aka ASP, Calmbp1, MCPH5}, Rexo2 (RNA exonuclease 2) [NCBI Gene 104444] {aka 1810038D15Rik, Rex2, Sfn, Smfn}, Dlk1 (delta like non-canonical Notch ligand 1) [NCBI Gene 13386] {aka DLK-1, DlkI, FA1, Ly107, Peg9, SCP1}, Gpm6a (glycoprotein m6a) [NCBI Gene 234267] {aka Gpm6, M6A}, Acta1 (actin alpha 1, skeletal muscle) [NCBI Gene 11459] {aka Acta-2, Acts, Actsk-1}, PLK1 (polo like kinase 1) [NCBI Gene 5347] {aka PLK, STPK13}, PI16 (peptidase inhibitor 16) [NCBI Gene 221476] {aka CD364, CRISP9, MSMBBP, PSPBP}, AVPR1A (arginine vasopressin receptor 1A) [NCBI Gene 552] {aka AVPR V1a, AVPR1, V1aR}
- **Diseases:** inflammation (MESH:D007249), bladder conditions (MESH:C566834), urothelial (MESH:D014526), GUDMAP (MESH:D000091642), chronic bacteriuria (MESH:D001437), Bladder cancer (MESH:D001749), age (MESH:D019588), congenital genitourinary malformations (MESH:D014564), UTI (MESH:D014552), cancer (MESH:D009369), benign bladder diseases (MESH:D001745), autoimmune disorders (MESH:D001327)
- **Chemicals:** luminal (MESH:D010634), tricarboxylic acid (MESH:D014233), paraffin (MESH:D010232), poly(A) (MESH:D011061), glycosaminoglycan (MESH:D006025), Formalin (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594)

## Full text

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## References

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Source: https://tomesphere.com/paper/PMC12870175