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Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin(-)SCA-1(+)CD49f(+)TROP2(high) phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin(-)CD49f(+)TROP2(high) PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin.
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http://dx.doi.org/10.1016/j.stemcr.2015.01.015 | DOI Listing |
Genome Biol
September 2025
Department of Evolutionary Genetics, Max-Planck Institute for Evolutionary Biology, Plön, Germany.
Background: Most RNA-seq datasets harbor genes with extreme expression levels in some samples. Such extreme outliers are usually treated as technical errors and are removed from the data before further statistical analysis. Here we focus on the patterns of such outlier gene expression to investigate whether they provide insights into the underlying biology.
View Article and Find Full Text PDFSci China Life Sci
September 2025
State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Labora
Histone arginine methylation by protein arginine methyltransferases (PRMTs) is crucial for transcriptional regulation and is implicated in cancers. Despite their therapeutic potential, some PRMTs present challenges as drug targets due to their context-dependent activities. Here, we demonstrate that hypoxia triggers the rapid condensation of PRMT2, which is essential for its histone H3R8 asymmetric dimethylation (H3R8me2a) activity.
View Article and Find Full Text PDFEMBO J
September 2025
Department of Infectious Diseases, Medical Research Institute, Zhongnan Hospital of Wuhan University; Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences; Wuhan University, Wuhan, 430071, China.
Inadequate antigen presentation by MHC-I in tumor microenvironment (TME) is a common immune escape mechanism. Here, we show that glycine decarboxylase (GLDC), a key enzyme in glycine metabolism, functions as an inhibitor of MHC-I expression in EGFR-activated tumor cells to induce immune escape by a mechanism independent of its enzymatic activity. Upon EGFR activation, GLDC is phosphorylated by SRC and subsequently translocated to the nucleus in human NSCLC cells.
View Article and Find Full Text PDFNat Immunol
September 2025
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
CD4 T follicular helper (T) cells support tailored B cell responses against multiple classes of pathogens. To reveal how diverse T phenotypes are established, we profiled mouse T cells in response to viral, helminth and bacterial infection. We identified a core T signature that is distinct from CD4 T follicular regulatory and effector cells and identified pathogen-specific transcriptional modules that shape T function.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, 100071, Beijing, China.
Traditional live attenuated vaccines (LAVs) are typically developed through serial passaging or genetic engineering to introduce specific mutations or deletions. While viral RNA secondary or tertiary structures have been well-documented for their multiple functions, including binding with specific host proteins, their potential for LAV design remains largely unexplored. Herein, using Zika virus (ZIKV) as a model, we demonstrate that targeted disruption of the primary sequence or tertiary structure of a specific viral RNA element responsible for Musashi-1 (MSI1) binding leads to a tissue-specific attenuation phenotype in multiple animal models.
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