General Information
- Project ID
- OEP003997
- Project Name
- Intermediate cell population depends on JAK/STAT signaling in prostate basal cell fates determination
- Description
- Many glandular epithelia, such as the prostate gland, consist of basal and luminal cells maintained by unipotent stem cells that can revert to multipotency during inflammation or cancer context. However, the defined basal stem cell populations responsible for prostate regeneration and their cell fates in prostate homeostasis, inflammation and carcinogenesis remain unclear. Using a genetic proliferation tracer (ProTracer) system, we found that basal cells exhibited extensive cell turnover during androgen-mediated prostate regression and regeneration. A rare intermediate basal cell population with luminal marker-expressing (termed Basal-B) and a large basal cell population (termed Basal-A) were identified in mouse prostates. Basal-B cells exhibited a greater capacity for organoid formation and luminal cell differentiation in vitro. Genetic lineage tracing showed that Basal-B cell maintained Basal-B cell identity and differentiated to Basal-A cell during androgen-mediated prostate regeneration. Specifically, Basal-B cells showed activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Inhibiting JAK/STAT signaling markedly reduced the proportion of Basal-B cells in normal mouse prostates. Fate-mapping results showed that Basal-B cells had a greater tendency to generate luminal cells during prostate inflammation. Whereas, JAK/STAT signaling inhibition notably attenuated the efficiency of basal-to-luminal differentiation of Basal-B cells during prostate inflammation. Additionally, deleting the Pten gene in basal cells significantly increased the Nkx3.1-expressing Basal-B like cell population and led to prostatic intraepithelial neoplasia. In humans, Basal-B cells were significantly more prevalent in benign prostate hyperplasia than in normal samples. Our findings identify Basal-B cells as a potential stem cell population and highlight JAK/STAT signaling as a key regulator in determining the cell fates of prostate intermediate Basal-B cells under both physiological and pathological conditions.
Project information
- Experiments
- 7
Experiment ID Experiment name Experiment type Create Date OEX022141 Basal-B Transcriptomic 2023-03-09 OEX027312 10X_2W_E-coli Transcriptomic 2024-02-23 OEX027313 10X_Day2_Pten Genomic 2024-02-23 OEX027314 10X_1W_Pten Genomic 2024-02-23 OEX027315 10X_2W_Pten Genomic 2024-02-23 OEX027316 hollow organoids derived Basal-A,Basal-B,Luminal Genomic 2024-02-23 OEX027317 10X_WT Genomic 2024-02-23 - Samples
- 7
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES297446 Basal-B Animalia Mus Prostate 2023-03-09 OES356382 10X_2W_Ecoli Animalia Mus musculus Prostate 2024-02-23 OES356383 10X_Day2_Pten Animalia Mus musculus Prostate 2024-02-23 OES356384 10X_1W_Pten Animalia Mus musculus Prostate 2024-02-23 OES356385 10X_2W_Pten Animalia Mus musculus Prostate 2024-02-23 OES356386 Organoids derived from basal-A, basal-B, and luminal Animalia Mus musculus Prostate 2024-02-23 OES356387 10X_WT Animalia Mus musculus Prostate 2024-02-23 - Runs
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7
Run ID Run Name Experiment Sample Data Num Create Date OER381608 OER_Lin_2303091041 OEX022141 OES297446 6 2023-03-09 OER459839 OER_Lin_2402231326 OEX027312 OES356382 8 2024-02-23 OER459840 OER_Lin_2402231328 OEX027313 OES356383 4 2024-02-23 OER459841 OER_Lin_2402231328 OEX027314 OES356384 4 2024-02-23 OER459842 OER_Lin_2402231329 OEX027315 OES356385 3 2024-02-23 OER459843 OER_Lin_2402231329 OEX027316 OES356386 18 2024-02-23 OER459844 OER_Lin_2402231559 OEX027317 OES356387 8 2024-02-23
Author Information
- Create Date
- 2023-03-09
- Last Modified
- 2024-02-26
- Submission
- Lin Li
- Shanghai Institutes for Biological Sciences