title: Defined conditions for the isolation and expansion of basal prostate progenitor cells of mouse and human origin.
abstract: 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.
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfner
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eisen
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Klein
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rigo-Watermeier
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Goeppinger
authors.affiliation: Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.affiliation: Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schoell
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vogel
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Noll
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany.
authors.forename: Irène
authors.initials: I
authors.lastname: Baccelli
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schillert
authors.affiliation: Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Steve
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Urology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Pahernik
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany. Electronic address: martin.sprick@hi-stem.de.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Sprick
authors.affiliation: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120 Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. Electronic address: a.trumpp@dkfz.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D000066673:Cell Self Renewal; D002469:Cell Separation / Q000379:methods; D016895:Culture Media, Serum-Free; D020869:Gene Expression Profiling; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction; D018038:Sodium Selenite / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D018038:Sodium Selenite