Identification of multipotent luminal progenitor cells in human prostate organoid cultures
By W. Karthaus, Phillip J. Iaquinta, J. Drost, A. Gračanin, R. van Boxtel, John Wongvipat, C. Dowling, D. Gao, H. Begthel, Norman Sachs and 5 more. Cell, 2014
680 citations recorded by the source corpus.
Summary The prostate gland consists of basal and luminal cells arranged as pseudo-stratified epithelium. In tissue recombination models, only basal cells reconstitute a complete prostate gland, yet murine lineage-tracing experiments show that luminal cells generate basal cells. It has remained challenging to address the molecular details of these transitions and whether they apply to humans, due to the lack of culture conditions that recapitulate prostate gland architecture. Here we describe a 3D culture system that supports long-term expansion of primary mouse and human prostate organoids, composed of fully differentiated CK5+ basal and CK8+ luminal cells. Organoids are genetically stable, reconstitute prostate glands in recombination assays and can be experimentally manipulated. Single human luminal and basal cells give rise to organoids, yet luminal cell-derived organoids more closely resemble prostate glands. These data support a luminal multilineage progenitor cell model for prostate tissue and establish a robust, scalable system for mechanistic studies.
Subfields: Pulmonary and Respiratory Medicine, Reproductive Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/085c0f16a18ca63be25e7c243bf1f0b85ad6125d
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Citations in the corpus
- Wnt/ b -Catenin Signaling, Disease, and Emerging Therapeutic Modalities (2017, background): “…(Huch et al., 2013b, 2015), pancreas (Boj et al., 2015; Huch et al., 2013a), prostate (Boj et al., 2015; Chua et al., 2014; Huch et al., 2013a; Karthaus et al., 2014), taste buds (Ren et al., 2014), inner ear (McLean et al., 2017), esophagus (DeWard et al., 2014), fallopian tube epithelium…”
- Long‐term expanding human airway organoids for disease modeling (2019, positive): “We have previously observed that remnants of normal epithelium in carcinoma samples will rapidly overgrow tumor tissue (Karthaus et al , 2014; van de Wetering et al , 2015).”
- Organoid cultures derived from patients with advanced prostate cancer (2014, neutral): “…NY 10065, USA 11Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA 12Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA 13Co-first authors *Correspondence: cheny1@mskcc.org (Y.C.), sawyersc@mskcc.org (C.L.S.) http://dx.doi.org/10.1016/j.cell.2014.08.016”
- Genetics and biology of prostate cancer (2018, background): “2014), normal mouse and human prostate epithelia (Karthaus et al. 2014), and self-organizing stem cells from mouse CARNs (castration-resistant Nkx3.”
- Modeling Development and Disease with Organoids. (2016, background): “Long-term cultured organoids were genetically stable and reconstitute prostate glands in recombination assays (Karthaus et al., 2014).”
- Organoid Models of Human and Mouse Ductal Pancreatic Cancer (2014, background): “…organoids by modifying approaches we previously pioneered to culture intestinal (Sato et al., 2009), gastric (Barker et al., 2010), colon carcinoma (Sato et al., 2011), hepatic (Huch et al., 2013b), pancreatic (Huch et al., 2013a), and prostatic organoids (Gao et al., 2014; Karthaus et al., 2014).”