@article{4f5f354613f84fe3a9991981926791f5,
title = "Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate",
abstract = "Aging is associated with loss of tissue mass and a decline in adult stem cell function in many tissues. In contrast, aging in the prostate is associated with growth-related diseases including benign prostatic hyperplasia (BPH). Surprisingly, the effects of aging on prostate epithelial cells have not been established. Here we find that organoid-forming progenitor activity of mouse prostate basal and luminal cells is maintained with age. This is caused by an age-related expansion of progenitor-like luminal cells that share features with human prostate luminal progenitor cells. The increase in luminal progenitor cells may contribute to greater risk for growth-related disease in the aging prostate. Importantly, we demonstrate expansion of human luminal progenitor cells in BPH. In summary, we define a Trop2+ luminal progenitor subset and identify an age-related shift in the luminal compartment of the mouse and human prostate epithelium. Aging is a significant risk factor for BPH and prostate cancer, but how aging increases disease risk in the prostate remains poorly defined. Crowell et al. show that progenitor-enriched luminal cells are expanded with aging in the mouse and human prostate, and may contribute to BPH.",
keywords = "aging, basal, epithelium, luminal, organoid, progenitor",
author = "Crowell, {Preston D.} and Fox, {Jonathan J.} and T. Hashimoto and Diaz, {Johnny A.} and Navarro, {H{\'e}ctor I.} and Henry, {Gervaise H.} and Feldmar, {Blake A.} and Lowe, {Matthew G.} and Garcia, {Alejandro J.} and Wu, {Ye E.} and Sajed, {Dipti P.} and Strand, {Douglas W.} and Goldstein, {Andrew S.}",
note = "Funding Information: We thank the families of organ donors at the Southwest Transplant Alliance for their commitment to basic science research. Special thanks to Donghui Cheng for cell sorting, Jack Mottahedeh for mouse work, Tom Carmichael and Stacey Gallegos for aged mice, Enca Montecino-Rodriguez and Ken Dorshkind for high-fat-diet mice, and Miriam Guemes for CyTOF sample acquisition. Mass cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility that is supported by NIH awards P30 CA016042 and 5P30 AI028697 . The purchase of the Helios/CyTOF mass cytometer that was used in this work was, in part, supported by funds provided by the James B. Pendleton Charitable Trust . J.J.F. is supported by a scholarship from the UCLA Minor in Biomedical Research and the Silva Endowment as part of the Undergraduate Research Scholars Program at UCLA. P.D.C. and M.G.L. are supported by the Ruth L. Kirschstein National Research Service Award GM007185 . H.I.N. is supported by the Eugene V. Cota-Robles Fellowship . J.A.D. is supported by the National Institute of General Medical Sciences of the NIH ( R25GM055052 awarded to T. Hasson) and the Saul Martinez Scholarship . A.S.G. is supported by the Spitzer Family Foundation Fund and the Gill Endowment . This work was supported by the American Cancer Society ( RSG-17-068-01-TBG ), Department of Defense ( W81XWH-13-1-0470 ), Margaret E. Early Medical Research Trust , STOP CANCER , NIH/NCI ( P50CA092131 /UCLA SPORE in Prostate Cancer), UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Rose Hills Foundation Innovator Grant, and support from UCLA's Jonsson Comprehensive Cancer Center , Broad Stem Cell Research Center , Clinical and Translational Science Institute , and Institute of Urologic Oncology . D.W.S. is supported by the NIH/NIDDK ( R01 DK115477 ). We thank UCLA{\textquoteright}s Technology Center for Genomics and Bioinformatics, Translational Pathology Core Laboratories, and UCLA{\textquoteright}s Institute for Quantitative and Computational Biology. The anti-alpha-tubulin monoclonal antibody (12G10) was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA. Funding Information: We thank the families of organ donors at the Southwest Transplant Alliance for their commitment to basic science research. Special thanks to Donghui Cheng for cell sorting, Jack Mottahedeh for mouse work, Tom Carmichael and Stacey Gallegos for aged mice, Enca Montecino-Rodriguez and Ken Dorshkind for high-fat-diet mice, and Miriam Guemes for CyTOF sample acquisition. Mass cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center (JCCC) and Center for AIDS Research Flow Cytometry Core Facility that is supported by NIH awards P30 CA016042 and 5P30 AI028697. The purchase of the Helios/CyTOF mass cytometer that was used in this work was, in part, supported by funds provided by the James B. Pendleton Charitable Trust. J.J.F. is supported by a scholarship from the UCLA Minor in Biomedical Research and the Silva Endowment as part of the Undergraduate Research Scholars Program at UCLA. P.D.C. and M.G.L. are supported by the Ruth L. Kirschstein National Research Service Award GM007185. H.I.N. is supported by the Eugene V. Cota-Robles Fellowship. J.A.D. is supported by the National Institute of General Medical Sciences of the NIH (R25GM055052 awarded to T. Hasson) and the Saul Martinez Scholarship. A.S.G. is supported by the Spitzer Family Foundation Fund and the Gill Endowment. This work was supported by the American Cancer Society (RSG-17-068-01-TBG), Department of Defense (W81XWH-13-1-0470), Margaret E. Early Medical Research Trust, STOP CANCER, NIH/NCI (P50CA092131/UCLA SPORE in Prostate Cancer), UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Rose Hills Foundation Innovator Grant, and support from UCLA's Jonsson Comprehensive Cancer Center, Broad Stem Cell Research Center, Clinical and Translational Science Institute, and Institute of Urologic Oncology. D.W.S. is supported by the NIH/NIDDK (R01 DK115477). We thank UCLA's Technology Center for Genomics and Bioinformatics, Translational Pathology Core Laboratories, and UCLA's Institute for Quantitative and Computational Biology. The anti-alpha-tubulin monoclonal antibody (12G10) was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA. P.D.C. J.J.F. T.H. J.A.D. H.I.N. B.A.F. and M.G.L. conducted the experiments. P.D.C. J.J.F. and A.S.G. designed the experiments. P.D.C. J.J.F. and A.S.G. wrote and edited the manuscript. Y.E.W. performed bioinformatics analyses and wrote part of the manuscript. A.J.G. assisted with CyTOF samples and wrote part of the manuscript. D.P.S. provided pathology expertise and wrote part of the manuscript. G.H.H. and D.W.S. performed human prostate experiments and wrote part of the manuscript. A.S.G. procured funding and supervised the experiments. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = aug,
day = "6",
doi = "10.1016/j.celrep.2019.07.007",
language = "English (US)",
volume = "28",
pages = "1499--1510.e6",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}