Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate

Preston D Crowell; Jonathan J Fox; Takao Hashimoto; Johnny A Diaz; Héctor I Navarro; Gervaise H Henry; Blake A Feldmar; Matthew G Lowe; Alejandro J Garcia; Ye E Wu; Dipti P Sajed; Douglas W Strand; Andrew S Goldstein

doi:10.1016/j.celrep.2019.07.007

Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate

Cell Rep. 2019 Aug 6;28(6):1499-1510.e6. doi: 10.1016/j.celrep.2019.07.007.

Affiliations

¹ Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Urology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
⁴ Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: [email protected].

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.

Keywords: aging; basal; epithelium; luminal; organoid; progenitor.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aging / pathology*
Animals
Antigens, Neoplasm / metabolism
Cell Adhesion Molecules / metabolism
Cell Proliferation
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Organoids / pathology
Prostate / pathology*
Prostatic Hyperplasia / pathology*
Stem Cells / pathology*
Young Adult

Substances

Antigens, Neoplasm
Cell Adhesion Molecules
TROP2 protein, mouse

Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Grants and funding