Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone
Abstract Background Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases. Methods Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single‐cell RNA‐sequencing. Result...
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.1084 |
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| author | Qiuxia Yan Miao Wang Haoran Xia Cao Dai Tongxiang Diao Yingfei Wang Huimin Hou Hong Zhang Ming Liu Xingbo Long |
| author_facet | Qiuxia Yan Miao Wang Haoran Xia Cao Dai Tongxiang Diao Yingfei Wang Huimin Hou Hong Zhang Ming Liu Xingbo Long |
| author_sort | Qiuxia Yan |
| collection | DOAJ |
| description | Abstract Background Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases. Methods Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single‐cell RNA‐sequencing. Results were validated by immunofluorescence staining. Results We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro‐stems but lower androgen‐related genes. These cells were primarily found in the TZ and provided a stem‐like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elevated MYC and E2F pathway activities was observed, primarily in the PZ. Further analysis revealed that epithelial cells in the TZ had higher levels of stem‐ and inflammation‐related pathway activities but lower androgen/lineage‐related pathway activities than those in the PZ. Notably, the activation of MYC, E2F and DNA repair pathways significantly increased in PZ luminal cells. In the immune landscape, we found that the immune microenvironment in the TZ is more complex and disordered with more infiltration of NK and Treg cells. CD8 T cell and macrophage in the TZ exhibit both inflammation activation and suppression phenotypes. In the stroma, the TZ had a higher fibroblast density, and fibroblasts in the TZ exhibited stronger transcriptome activity in immunity and proliferation. Ligand–receptor interaction analysis revealed that fibroblasts could contribute to a NOTCH signaling niche for club/hillock cells in the TZ and balance the prostate immune microenvironment. The activation of stem properties, inflammatory infiltration and loss of androgen/lineage activity are prominent features distinguishing the TZ from PZ. Conclusions Our study explains the heterogeneity between the TZ and PZ of aged prostate, which may help understand the spatial distribution of prostate diseases and establish a foundation for novel target discovery. |
| first_indexed | 2024-04-12T11:09:06Z |
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| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-12T11:09:06Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-68c862751ba541cd97b794e2466ebaed2022-12-22T03:35:40ZengWileyClinical and Translational Medicine2001-13262022-10-011210n/an/a10.1002/ctm2.1084Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zoneQiuxia Yan0Miao Wang1Haoran Xia2Cao Dai3Tongxiang Diao4Yingfei Wang5Huimin Hou6Hong Zhang7Ming Liu8Xingbo Long9Peking University Fifth School of Clinical Medicine Beijing ChinaDepartment of Urology Beijing Hospital National Center of Gerontology Beijing ChinaDepartment of Urology Beijing Hospital National Center of Gerontology Beijing ChinaDepartment of General Surgery The Third Affiliated Hospital Sun Yat‐sen University Guangzhou Guangdong ChinaDepartment of Urology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan ChinaBeijing Hongying Primary School Beijing ChinaDepartment of Urology Beijing Hospital National Center of Gerontology Beijing ChinaInstitute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences Peking University Health Science Center Beijing ChinaDepartment of Urology Beijing Hospital National Center of Gerontology Beijing ChinaDepartment of Urology Sun Yat‐sen University Cancer Center Guangzhou Guangdong ChinaAbstract Background Identifying cellular and functional heterogeneity within aged prostate is critical for understanding the spatial distribution of prostate diseases. Methods Aged human prostate peripheral zone (PZ) and transitional zone (TZ) tissues were used for single‐cell RNA‐sequencing. Results were validated by immunofluorescence staining. Results We found that club/hillock epithelial cells, compared with other epithelial cells, had significantly higher NOTCH signaling activity and expressed higher levels of neuro‐stems but lower androgen‐related genes. These cells were primarily found in the TZ and provided a stem‐like niche around the proximal prostate ducts. Significant heterogeneity was observed in the aged luminal population. A novel TFF3+ luminal subtype with elevated MYC and E2F pathway activities was observed, primarily in the PZ. Further analysis revealed that epithelial cells in the TZ had higher levels of stem‐ and inflammation‐related pathway activities but lower androgen/lineage‐related pathway activities than those in the PZ. Notably, the activation of MYC, E2F and DNA repair pathways significantly increased in PZ luminal cells. In the immune landscape, we found that the immune microenvironment in the TZ is more complex and disordered with more infiltration of NK and Treg cells. CD8 T cell and macrophage in the TZ exhibit both inflammation activation and suppression phenotypes. In the stroma, the TZ had a higher fibroblast density, and fibroblasts in the TZ exhibited stronger transcriptome activity in immunity and proliferation. Ligand–receptor interaction analysis revealed that fibroblasts could contribute to a NOTCH signaling niche for club/hillock cells in the TZ and balance the prostate immune microenvironment. The activation of stem properties, inflammatory infiltration and loss of androgen/lineage activity are prominent features distinguishing the TZ from PZ. Conclusions Our study explains the heterogeneity between the TZ and PZ of aged prostate, which may help understand the spatial distribution of prostate diseases and establish a foundation for novel target discovery.https://doi.org/10.1002/ctm2.1084aged prostatebenign prostatic hyperplasiaheterogeneityNOTCH signalingprostate cancersingle‐cell RNA‐sequencing |
| spellingShingle | Qiuxia Yan Miao Wang Haoran Xia Cao Dai Tongxiang Diao Yingfei Wang Huimin Hou Hong Zhang Ming Liu Xingbo Long Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone Clinical and Translational Medicine aged prostate benign prostatic hyperplasia heterogeneity NOTCH signaling prostate cancer single‐cell RNA‐sequencing |
| title | Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| title_full | Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| title_fullStr | Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| title_full_unstemmed | Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| title_short | Single‐cell RNA‐sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| title_sort | single cell rna sequencing technology demonstrates the heterogeneity between aged prostate peripheral and transitional zone |
| topic | aged prostate benign prostatic hyperplasia heterogeneity NOTCH signaling prostate cancer single‐cell RNA‐sequencing |
| url | https://doi.org/10.1002/ctm2.1084 |
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