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

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 sin...

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Autores principales:	Hongzhen Li, Vijender Chaitankar, Jianqiong Zhu, Kyung Chin, Wenli Liu, Mehdi Pirooznia, Griffin P. Rodgers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5a03d97bd48c4b5caa31ae643b050fb3
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spelling	oai:doaj.org-article:5a03d97bd48c4b5caa31ae643b050fb32021-12-02T13:34:00ZOlfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC10.1038/s41598-020-78774-52045-2322https://doaj.org/article/5a03d97bd48c4b5caa31ae643b050fb32020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78774-5https://doaj.org/toc/2045-2322Abstract 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.Hongzhen LiVijender ChaitankarJianqiong ZhuKyung ChinWenli LiuMehdi PiroozniaGriffin P. RodgersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hongzhen Li Vijender Chaitankar Jianqiong Zhu Kyung Chin Wenli Liu Mehdi Pirooznia Griffin P. Rodgers Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
description	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.
format	article
author	Hongzhen Li Vijender Chaitankar Jianqiong Zhu Kyung Chin Wenli Liu Mehdi Pirooznia Griffin P. Rodgers
author_facet	Hongzhen Li Vijender Chaitankar Jianqiong Zhu Kyung Chin Wenli Liu Mehdi Pirooznia Griffin P. Rodgers
author_sort	Hongzhen Li
title	Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
title_short	Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
title_full	Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
title_fullStr	Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
title_full_unstemmed	Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC
title_sort	olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via myc
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5a03d97bd48c4b5caa31ae643b050fb3
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Olfactomedin 4 mediation of prostate stem/progenitor-like cell proliferation and differentiation via MYC

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