News
New Single-Cell and Spatial Datasets on Human Ureter and Prostate Tissue by Angela Ting and Douglas Strand (GUDMAP)
Sep 4, 2024
We are excited to announce GUDMAP’s release of two new single-cell and spatial transcriptomic datasets from recent studies on the human ureter and prostate. The first dataset, from the study led by Angela Ting at MD Anderson Cancer Center, provides a detailed map of cell populations and signaling networks within the human ureter, with a focus on stromal and urothelial compartments. The second, from Doug Strand at UT Southwestern, explores the effects of 5-alpha reductase inhibitors on prostate tissue, revealing the transition of prostate luminal cells to a club cell-like state in response to treatment.
Single-cell and spatial mapping Identify cell types and signaling Networks in the human ureter (PI: Angela Ting, MDACC)
Related publication:
Single-cell and spatial mapping Identify cell types and signaling Networks in the human ureter, Developmental Cell, 2022, 57 (15) 1899-1916, https://www.doi.org/10.1016/j.devcel.2022.07.004
We define and spatially map cell populations within the human ureter using single-cell RNA sequencing, spatial gene expression, and immunofluorescence approaches. We focus on the stromal and urothelial cell populations to enumerate the distinct cell types composing the human ureter and infer potential cell-cell communication networks underpinning the bi-directional crosstalk between these compartments. Furthermore, we analyze and experimentally validate the importance of the sonic hedgehog (SHH) signaling pathway in adult progenitor cell maintenance. The SHH-expressing basal cells support organoid generation in vitro and accurately predict the differentiation trajectory from basal progenitor cells to terminally differentiated umbrella cells.
5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia (PI: Doug Strand, UTSW)
Related publication:
5-Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia, Journal of Pathology, 2022, 256 (4) 427-441, 34928497, 10.1002/path.5857, https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.5857
Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
