| 36 | 0 | 6 |
| 下载次数 | 被引频次 | 阅读次数 |
良性前列腺增生（Benign prostatic hyperplasia，BPH）是老年男性常见疾病，其病理机制尚未完全阐明。这主要归咎于BPH致病过程中的核心驱动细胞尚不明确。近年来，单细胞RNA测序技术（single-cell RNA sequencing，scRNA-seq）的出现，显著推动了BPH关键细胞类型及其功能、发育轨迹和细胞间相互作用的精准解析。基于此，本研究将通过系统梳理基于单细胞转录组学的BPH分子机制的最新研究进展，为后续相关研究及新治疗策略的开发提供新的理论框架。
Abstract：Benign prostatic hyperplasia (BPH) is a prevalent condition among aging men， yet its underlying pathological mechanisms remain incompletely elucidated， largely due to uncertainty regarding the identity and role of key driver cell populations in disease initiation and progression. In recent years， the emergence of single-cell RNA sequencing technology (Single-cell RNA sequencing， scRNA-seq) has significantly advanced the precise analysis of key cell types， as well as their functions， developmental trajectories， and intercellular interactions in BPH. Based on this， this review will systematically summarize the latest research progress on the molecular mechanisms of BPH from the perspective of singl-cell transcriptomics， providing a new theoretical framework for subsequent related research and the development of new treatment strategies.
Anon， 2021. Method of the Year 2020: spatially resolved transcriptomics. Nat. Methods， 18(1): 1.
ARAN D， LOONEY A P， LIU L Q， et al.， 2019. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol.， 20(2): 163-172.
BANDYOPADHYAY S， DUFFY M P， AHN K J， et al.， 2024. Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging. Cell， 187(12): 3120-3140.e29.
BROMAN M M， LANMAN N A， VICKMAN R E， et al.， 2025. Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia. Front. Immunol.， 16: 1585446.
BUSETTO G M， LOMBARDO R， DE NUNZIO C， et al.， 2025. Ejaculation sparing of classic and minimally invasive surgical treatments of LUTS/BPH. Prostate Cancer Prostatic Dis.， 28(1): 37-44.
CAO D H， SUN R N， PENG L， et al.， 2022. Immune cell proinflammatory microenvironment and androgen-related metabolic regulation during benign prostatic hyperplasia in aging. Front. Immunol.， 13: 842008.
CAO T Y， XIE F， SHI Y W， et al.， 2023. Rapamycin and low-dose IL-2 mediate an immunosuppressive microenvironment to inhibit benign prostatic hyperplasia. Int. J. Biol. Sci.， 19(11): 3441-3455.
CHEN J， WANG X， MA A， et al.， 2022. Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data. Nat. Commun.， 13(1): 6494.
CHEN L， LIU Y， YUE S Y， et al.， 2024. P2X7R modulates NEK7-NLRP3 interaction to exacerbate experimental autoimmune prostatitis via GSDMD-mediated prostate epithelial cell pyroptosis. Int. J. Biol. Sci.， 20(9): 3393-3411.
CHEN X， YANG S Y， HE Z X， et al.， 2025. Comprehensive analysis of the global， regional， and national burden of benign prostatic hyperplasia from 1990 to 2021. Sci. Rep.， 15(1): 5644.
CHIU P K， CHAN C H， LIU A Q， et al.， 2023. A prospective evaluation of the effect of finasteride on prostate health index (phi). Int. Urol. Nephrol.， 55(5): 1087-1092.
DOMíNGUEZ CONDE C， XU C， JARVIS L B， et al.， 2022. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science， 376(6594): eabl5197.
DOS SANTOS L， CARBONE F， PACREAU E， et al.， 2024. Cell plasticity in a mouse model of benign prostate hyperplasia drives amplification of androgen-independent epithelial cell populations sensitive to antioxidant therapy. Am. J. Pathol.， 194(1): 30-51.
EFREMOVA M， VENTO-TORMO M， TEICHMANN S A， et al.， 2020. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc.， 15(4): 1484-506.
FAN C， CHEN F， CHEN Y， et al.， 2024. irGSEA: the integration of single-cell rank-based gene set enrichment analysis. Brief. Bioinform.， 25(4): bbae243.
FEI X W， LIU J C， XU J Y， et al.， 2024. Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia. J. Transl. Med.， 22(1): 380.
FRANZEN O， GAN LM， BJORKEGREN J L M， 2019. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford)， 2019: baz046.
FU X， LIU J M， LIU D Q， et al.， 2022. Glucose-regulated protein 78 modulates cell growth， epithelial–mesenchymal transition， and oxidative stress in the hyperplastic prostate. Cell Death Dis.， 13: 78.
GAO T T， ZHAO P， HAN S X， 2025. Integrating bulk RNA-seq and scRNA-seq analyses with machine learning to predict platinum response and prognosis in ovarian cancer. Sci. Rep.， 15(1): 19123.
GAO Y Z， ZHANG X P， XIA S L， et al.， 2025. Spatial multi-omics reveals the potential involvement of SPP1~(+) fibroblasts in determining metabolic heterogeneity and promoting metastatic growth of colorectal cancer liver metastasis. Mol. Ther.， 33(8): 3680-3700.
GBD 2019 Benign Prostatic Hyperplasia Collaborators， 2022. The global， regional， and national burden of benign prostatic hyperplasia in 204 countries and territories from 2000 to 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Healthy Longev.， 3(11): e754-e776.
HAMILTON R J， CHAVARRIAGA J， KHURRAM N， et al.， 2024. 5-α reductase inhibitors and prostate cancer mortality. JAMA Netw. Open， 7(8): e2430223.
HATA J， HARIGANE Y， MATSUOKA K， et al.， 2023. Mechanism of androgen-independent stromal proliferation in benign prostatic hyperplasia. Int. J. Mol. Sci.， 24(14): 11634.
HE W， TIAN Z， DONG B， et al.， 2024. Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate. J. Transl. Med.， 22(1): 255.
HENRY G H， MALEWSKA A， JOSEPH D B， et al.， 2018. A cellular anatomy of the normal adult human prostate and prostatic urethra. Cell Rep.， 25(12): 3530-3542.e5.
HU C， LI T， XU Y， et al.， 2023. CellMarker 2.0: an updated database of manually curated cell markers in human/mouse and web tools based on scRNA-seq data. Nucleic Acids Res.， 51(D1): D870-D876.
HUANG Y， MOHANTY V， DEDE M， et al.， 2023. Characterizing cancer metabolism from bulk and single-cell RNA-seq data using METAFlux. Nat. Commun.， 14(1): 4883.
JIANG S， QIAN Q， ZHU T， et al.， 2023. Cell Taxonomy: a curated repository of cell types with multifaceted characterization. Nucleic Acids Res.， 51: D853-D860.
JIN B R， LIM C Y， KIM H J， et al.， 2023. Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR-NLRP3 pathway. Redox Biol.， 65: 102816.
JOSEPH D B， HENRY G H， MALEWSKA A， et al.， 2020. Urethral luminal epithelia are castration-insensitive cells of the proximal prostate. Prostate， 80(11): 872-884.
JOVIC D， LIANG X， ZENG H， et al.， 2022. Single-cell RNA sequencing technologies and applications: a brief overview. Clin. Transl. Med.， 12(3): e694.
KE D， CAO M， NI J， et al.， 2024. Macrophage and fibroblast trajectory inference and crosstalk analysis during myocardial infarction using integrated single-cell transcriptomic datasets. J. Transl. Med.， 22(1): 560.
LI J， SMALLEY I， CHEN Z， et al.， 2022. Single-cell characterization of the cellular landscape of acral melanoma identifies novel targets for immunotherapy. Clin. Cancer Res.， 28(10): 2131-2146.
LI J R， YAO H Y， HUANG J， et al.， 2022. METTL3 promotes prostatic hyperplasia by regulating PTEN expression in an m6A-YTHDF2-dependent manner. Cell Death Dis.， 13(8): 723.
LI S， ZHOU X W， FENG H Q， et al.， 2025. Deciphering the immunomodulatory function of GSN~(+) inflammatory cancer-associated fibroblasts in renal cell carcinoma immunotherapy: insights from pan-cancer single-cell landscape and spatial transcriptomics analysis. Cell Prolif.， 58(12): e70062.
LI Z， WANG X F， LIU Z F， et al.， 2025. Single-cell sequencing reveals that CD4~(+) T cells eliminate senescent prostate epithelium to delay progression of benign prostatic hyperplasia. Aging Cell， 24(10): e70180.
LIN Z M， FAN D D， JIN S， et al.， 2021. Methylated CpG dinucleotides in the 5-α reductase 2 gene may explain finasteride resistance in benign prostatic enlargement patients. Asian J. Androl.， 23(3): 266-272.
MENG F L， HUANG X L， QIN W Y， et al.， 2023. singleCellBase: a high-quality manually curated database of cell markers for single cell annotation across multiple species. Biomark. Res.， 11(1): 83.
MCCONNELL J D， BRUSKEWITZ R， WALSH P， et al.， 1998. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N. Engl. J. Med.， 338(9): 557-563.
MCCONNELL J D， ROEHRBORN C G， BAUTISTA O M， et al.， 2003. The long-term effect of doxazosin， finasteride， and combination therapy on the clinical progression of benign prostatic hyperplasia. N. Engl. J. Med.， 349(25): 2387-2398.
PARK W Y， SONG G， PARK J Y， et al.， 2022. Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3. Cell Death Dis.， 13(6): 554.
PING S， JIA X， TIAN Y N， 2025. Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer. J. Transl. Med.， 23(1): 795.
RAO A， BARKLEY D， FRAN?A G S， et al.， 2021. Exploring tissue architecture using spatial transcriptomics. Nature， 596(7871): 211-220.
REGNER M J， WISNIEWSKA K， GARCIA-RECIO S， et al.， 2021. A multi-omic single-cell landscape of human gynecologic malignancies. Mol. Cell.， 81(23): 4924-4941.e10.
RODRIQUES S G， STICKELS R R， GOEVA A， et al.， 2019. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science， 363(6434): 1463-1467.
SHARKEY C， LONG X B， AL-FAOURI R， et al.， 2024. Enhanced prostatic Esr1~(+) luminal epithelial cells in the absence of SRD5A2. J. Pathol.， 263(3): 300-314.
SHEN Y T， FEI X W， DAI L Y， et al.， 2025. Integrating spatial transcriptomics and single-cell RNA-sequencing reveals epithelial cell alterations in benign prostatic hyperplasia following finasteride treatment. Genes Dis.， 12(5): 101526.
SHEN Y T， FEI X W， XU J Y， et al.， 2023. Performance analysis of markers for prostate cell typing in single-cell data. Genes Dis.， 11(6): 101157.
SONG Z F， CHENG Z J， YUAN H， et al.， 2024. Correlation between benign prostatic hyperplasia and comorbidities: a systematic analysis integrating global burden of disease and Mendelian randomization study. J. Transl. Med.， 22(1): 1035.
SONG W， WANG Y T， ZHOU M， et al.， 2025. Spatial transcriptomics and scRNA-seq: decoding tumor complexity and constructing prognostic models in colorectal cancer. Hum. Genom.， 19(1): 92.
SRIVATSAN S R， REGIER M C， BARKAN E， et al.， 2021. Embryo-scale， single-cell spatial transcriptomics. Science， 373(6550): 111-117.
STREET K， RISSO D， FLETCHER R B， et al.， 2018. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics， 19(1): 477.
TAN Z， CHEN X， ZUO J， et al.， 2023. Comprehensive analysis of scRNA-Seq and bulk RNA-Seq reveals dynamic changes in the tumor immune microenvironment of bladder cancer and establishes a prognostic model. J. Transl. Med.， 21(1): 223.
TANG F， BARBACIORU C， WANG Y， et al.， 2009. mRNA-Seq whole-transcriptome analysis of a single cell. Nat. Methods， 6(5): 377-82.
TRAISH A M， 2020. Health risks associated with long-term finasteride and dutasteride use: it’s time to sound the alarm. World J. Men’s Health， 38(3): 323.
TRAPNELL C， CACCHIARELLI D， GRIMSBY J， et al.， 2014. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol.， 32(4): 381-386.
VELLKY J E， WU Y Q， MOLINE D， et al.， 2024. Single-cell RNA sequencing of human prostate basal epithelial cells reveals zone-specific cellular populations and gene expression signatures. J. Pathol.， 262(2): 212-225.
VICKOVIC S， ERASLAN G， SALMéN F， et al.， 2019. High-definition spatial transcriptomics for in situ tissue profiling. Nat. Meth.， 16(10): 987-990.
WANG R， ZHENG Q， GRAHAM M K， et al.， 2025. A transition zone enriched WIF1? basal cell subtype is associated with benign prostatic hyperplasia. bioRxiv [Preprint]， 2025.12.08.692826.
WANG Y C， ZHOU L， LIU J H， et al.， 2025. Elucidating cellular senescence-related genes in benign prostatic hyperplasia through Mendelian randomization and single-cell RNA sequencing. J. Gerontol. A Biol. Sci. Med. Sci.， 80(7): glaf073.
WANG Z K， LIU F J， YE S L， et al.， 2019. Plasma proteome profiling of high-altitude polycythemia using TMT-based quantitative proteomics approach. J. Proteomics， 194: 60-69.
WU E L， LIANG J H， ZHAO J X， et al.， 2025. Identification of potential shared gene signatures between periodontitis and breast cancer by integrating bulk RNA-seq and scRNA-seq data. Sci. Rep.， 15(1): 11216.
WU X Y， GU Y， LI L， 2017. The anti-hyperplasia， anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats. Toxicol. Lett.， 265: 9-16.
WU Y， ZHANG C， HUANG J C， et al.， 2025. Integrated analysis of scRNA-seq and bulk RNA-seq data identifies BHLHE40 as a key gene in pancreatic cancer progression and gemcitabine resistance. Semin. Oncol.， 52(2): 152338.
XU W W， LIANG T， FANG H， et al.， 2025. Single-cell RNA sequencing identifies MMP11~(+) cancer-associated fibroblasts as drivers of angiogenesis and bladder cancer progression. Adv. Sci.， 12(32): e02774.
ZHAN M， YANG R F， GU Y， et al.， 2025. Fibroblasts promote the progression of benign prostatic hyperplasia through colony-stimulating factor 1 receptor-mediated RTK signaling in prostatic epithelial cells. Mol. Biomed.， 6(1): 126.
ZHENG G X Y， TERRY J M， BELGRADER P， et al.， 2017. Massively parallel digital transcriptional profiling of single cells. Nat. Commun.， 8: 14049.
基本信息:
中图分类号:R697.3
引用信息:
[1]吴优,郭雨涵,沈彦婷,等.基于scRNA-seq技术的良性前列腺增生疾病研究进展[J].基因组学与应用生物学().
基金信息:
国家自然科学基金项目（82570908）; 上海市浦东新区卫生英才培养计划项目（2024PDWSYCQN-04）共同资助
2026-05-15
2026-05-15
2026-05-15