International Journal Of Bilogical Sciences
.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 9 > Dong-Kee Lee1, Yonghong Liu1,2, Lan Liao1, Fen Wang2, and Jianming Xu1,3
The Prostate Basal Cell (BC) Heterogeneity and the p63-Positive BC Differentiation Spectrum in Mice
Dong-Kee Lee1, Yonghong Liu1,2, Lan Liao1, Fen Wang2, and Jianming Xu1,3
1. Department of Molecular and Cellular Biology, Houston, Texas, USA; 2. Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, TX, USA; 3. Institute for Cancer Medicine, Luzhou Medical College, Luzhou, Sichuan, China. Corresponding author: Jianming Xu, PhD, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. Tele: 713-798-6199; Fax: 713-798- 3017; E-mail: firstname.lastname@example.org.
The prostate epithelium is composed of basal (BC), luminal (LEC), and neuroendocrine (NEC) cells. It is unclear how many subtypes of BCs in the prostate and which subtype of BCs contains the main stem cell niche in the adult prostate. Here we report seven BC subpopulations according to their p63, cytokeratin 14 (K14) and K5 expression patterns, including p63-positive/K14-negative/K5-negative (p63+/K14-/K5-), p63-/K14+/K5-, p63-/K14-/K5+, p63+/K14+/K5-, p63+/K14-/K5+, p63-/K14+/K5+, and p63+/K14+/K5+ BCs. We generated a p63-CreERT2 knock-in mouse line that expresses tamoxifen-inducible Cre activity in the p63-expressing cells, including the prostate BCs. We then crossbred this line with ROSA26R mice, and generated p63-CreERT2×ROSA26R bi-genic mice harboring the Cre-activated β-galactosidase reporter gene. We treated these bi-genic mice with tamoxifen to mark the p63+ BCs at different ages or under different hormonal conditions, and then traced the lineage differentiation of these genetically labeled BCs. We discovered that these p63+ BCs contain self-renewable stem cells in culture and efficiently differentiated into LECs, NECs and BCs in the postnatal, adult and re-generating mouse prostates. Therefore, BC population contains heterogeneous BCs that express different combinations of the p63, K14 and K5 differentiation markers. Because K14+ and K5+ BCs were previously shown to be extremely inefficient to produce LECs in adulthood, we propose that the p63+/K5-/K14- subpopulation of BCs contains most stem-like cells, especially in adult animals.
Prostate epithelium, basal cell differentiation, p63, lineage tracing, stem cell.
Date Deposited : 13 Feb 2016 10:47
Official URL: http://www.ijbs.com/v10i9
Last Modified : 13 Feb 2016 10:47
Volume 10, Number 9, - 2014 , ISSN 1449-2288
Full Text Original