International Journal of Molecular Sciences

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Ovarian Stem Cells

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Dear Colleagues,

In recent years, new therapeutic approaches are in high demand due to the increases in clinical symptoms which could be solved by a new source of female germ cells. The question of de novo synthesis of oocytes and the ability of pluripotent stem cells to differentiate into germ cells triggers the concept of “ovarian stem cells”.

The goal of this Special Issue is the communication of stem cell technology and concept of ovarian stem cells to new scientific disciplines regarding female germ cell generation.

The Special Issue includes various approaches to isolation and culture of female germ cells, stem cell differentiation into gametes, biomaterials for generation of female germ cells and tissue engineering for the generation of germ cells, in vivo models and therapeutic approach using stem cell-derived germ cells.

Original articles and reviews will be welcome for submission, and the fast peer-review process will enhance the impact of submitted articles.

Dr. Yoon Young Kim
Guest Editor

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Keywords

ovarian stem cells
female germ cells
stem cell differentiation
oocytes
stem cell therapy
reproductive biology
reproductive engineering

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Research

17 pages, 5834 KiB

Open AccessArticle

Epigenomic Profiling of Epithelial Ovarian Cancer Stem-Cell Differentiation Reveals GPD1 Associated Immune Suppressive Microenvironment and Poor Prognosis

by Lin-Yu Chen, Rui-Lan Huang, Po-Hsuan Su, Ling-Hui Chu, Yu-Chun Weng, Hui-Chen Wang, Hung-Cheng Lai and Kuo-Chang Wen

Int. J. Mol. Sci. 2022, 23(9), 5120; https://doi.org/10.3390/ijms23095120 - 4 May 2022

Cited by 3 | Viewed by 2308

Abstract

Intraperitoneal metastasis is a challenging clinical scenario in epithelial ovarian cancer (EOC). As they are distinct from hematogenous metastasizing tumors, epithelial ovarian cancer cells primarily disseminate within the peritoneal cavity to form superficially invasive carcinomas. Unfavorable pharmacokinetics for peritoneal tumors and gut toxicity collectively lead to a narrow therapeutic window and therefore limit the opportunities for a favorable clinical outcome. New insights into tumor metastasis in the peritoneal microenvironment are keenly awaited to develop new therapeutic strategies. Epithelial ovarian cancer stem cell (OCSC) seeding is considered to be a critical component of the peritoneal spread. Using a unique and stepwise process of the OCSC differentiation model may provide insight into the intraperitoneal metastasis. The transcriptome and epigenome of OCSC differentiation were characterized by expression array and MethylCap-Seq. The TCGA, AOCS, and KM-Plotter databases were used to evaluate the association between survival outcomes and the methylation/expression levels of candidate genes in the EOC datasets. The STRING database was used to investigate the protein–protein interaction (PPI) for candidates and their associated genes. The infiltration level of immune cells in EOC patients and the association between clinical outcome and OCSCs differentiation genes were estimated using the TIDE and TIME2.0 algorithms. We established an EOC differentiation model using OCSCs. After an integrated transcriptomics and methylomics analysis of OCSCs differentiation, we revealed that the genes associated with earlier OCSC differentiation were better able to reflect the patient’s outcome. The OCSC differentiation genes were involved in regulating metabolism shift and the suppressive immune microenvironment. High GPD1 expression with high pro-tumorigenic immune cells (M2 macrophage, and cancer associated fibroblast) had worst survival. Moreover, we developed a methylation signature, constituted by GNPDA1, GPD1, GRASP, HOXC11, and MSLN, that may be useful for prognostic prediction in EOC. Our results revealed a novel role of epigenetic plasticity OCSC differentiation and suggested metabolic and immune intervention as a new therapeutic strategy. Full article

(This article belongs to the Special Issue Ovarian Stem Cells)

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