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  • Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC.

Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC.

Scientific reports (2020-12-16)
Hongzhen Li, Vijender Chaitankar, Jianqiong Zhu, Kyung Chin, Wenli Liu, Mehdi Pirooznia, Griffin P Rodgers
ABSTRACT

Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4's physiological functions in these cells have not been elucidated. Using single-cell RNA sequencing analysis, we found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations in both the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the stem/progenitor-like cell population, shifts stem/progenitor-like cell division to favor symmetric division and differentiated into higher levels PSA expression cells in organoid assays compared with OLFM4-wild RWPE1 cells. Bulk-cell RNA sequencing analysis pinpointed that cMYC expression were enhanced in the OLFM4-knockout RWPE1 cells compared with OLFM4-wild cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate multiple biological processes, in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
5α-Androstan-17β-ol-3-one, ≥97.5%
Sigma-Aldrich
(+)-JQ1, ≥98% (HPLC)