From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells

Abstract With the significant challenges in using human embryonic stem cells (ESCs) for research and clinical applications, there is a growing impetus to seek alternative pluripotent cell sources. Embryonic stem-like (ES-like) cells emerge as a promising avenue in this pursuit. Our research demonstr...

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Main Authors: Nima Ghasemi, Hossein Azizi, Ali Qorbanee, Thomas Skutella
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Genomics
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Online Access:https://doi.org/10.1186/s12864-025-11612-y
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author Nima Ghasemi
Hossein Azizi
Ali Qorbanee
Thomas Skutella
author_facet Nima Ghasemi
Hossein Azizi
Ali Qorbanee
Thomas Skutella
author_sort Nima Ghasemi
collection DOAJ
description Abstract With the significant challenges in using human embryonic stem cells (ESCs) for research and clinical applications, there is a growing impetus to seek alternative pluripotent cell sources. Embryonic stem-like (ES-like) cells emerge as a promising avenue in this pursuit. Our research demonstrates the potential for deriving ES-like cells from spermatogonial stem cells (SSCs) in a time-dependent manner under defined culture conditions. To better understand this process, we investigated the gene expression dynamics and underlying pathways associated with ES-like cell generation from SSCs. A deeper understanding of the signaling pathways underlying this biological process can lead us to refine protocols for ES-like cell generation, which could catalyze the development of more efficient and expedited methodologies inspired by the derivation pathway for future research in regenerative medicine. To identify differentially expressed genes (DEGs), we analyzed publicly available microarray data from murine cells obtained from the Gene Expression Omnibus (GEO). This analysis enabled the prediction of protein–protein interactions (PPIs), which were subsequently used for pathway enrichment analysis to identify biologically relevant pathways. Complementing these computational findings, we conducted in vitro experiments, including Fluidigm qPCR and immunostaining. These experiments serve as validation for our microarray data and the DEGs identified, providing reassurance about the reliability of our research. Among the identified enriched pathways in our investigation are the Toll-like receptor (TLR), GDNF/RET, interleukins (ILs), FGF/FGFR, and SMAD signaling pathway, along with the activation of NIMA kinases. Additionally, miR-410-3p, miRNA let-7e, Miat, and Xist are among some of the predicted non-coding RNAs.
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spelling doaj-art-b6b01b09f8324a56ae81c63e8d2be9e02025-08-20T02:55:31ZengBMCBMC Genomics1471-21642025-04-0126111610.1186/s12864-025-11612-yFrom unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cellsNima Ghasemi0Hossein Azizi1Ali Qorbanee2Thomas Skutella3Department of Applied Biotechnology and System Biology, College of Biotechnology, Amol University of Special Modern TechnologiesDepartment of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern TechnologiesDepartment of Surgery, Faculty of General of Medicine, Koya UniversityInstitute for Anatomy and Cell Biology, Medical Faculty, University of HeidelbergAbstract With the significant challenges in using human embryonic stem cells (ESCs) for research and clinical applications, there is a growing impetus to seek alternative pluripotent cell sources. Embryonic stem-like (ES-like) cells emerge as a promising avenue in this pursuit. Our research demonstrates the potential for deriving ES-like cells from spermatogonial stem cells (SSCs) in a time-dependent manner under defined culture conditions. To better understand this process, we investigated the gene expression dynamics and underlying pathways associated with ES-like cell generation from SSCs. A deeper understanding of the signaling pathways underlying this biological process can lead us to refine protocols for ES-like cell generation, which could catalyze the development of more efficient and expedited methodologies inspired by the derivation pathway for future research in regenerative medicine. To identify differentially expressed genes (DEGs), we analyzed publicly available microarray data from murine cells obtained from the Gene Expression Omnibus (GEO). This analysis enabled the prediction of protein–protein interactions (PPIs), which were subsequently used for pathway enrichment analysis to identify biologically relevant pathways. Complementing these computational findings, we conducted in vitro experiments, including Fluidigm qPCR and immunostaining. These experiments serve as validation for our microarray data and the DEGs identified, providing reassurance about the reliability of our research. Among the identified enriched pathways in our investigation are the Toll-like receptor (TLR), GDNF/RET, interleukins (ILs), FGF/FGFR, and SMAD signaling pathway, along with the activation of NIMA kinases. Additionally, miR-410-3p, miRNA let-7e, Miat, and Xist are among some of the predicted non-coding RNAs.https://doi.org/10.1186/s12864-025-11612-ySpermatogonial stem cellsEmbryonic stem-like cellsMicroarray analysisPPI networkSignaling pathwaysmiRNA and lncRNA
spellingShingle Nima Ghasemi
Hossein Azizi
Ali Qorbanee
Thomas Skutella
From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
BMC Genomics
Spermatogonial stem cells
Embryonic stem-like cells
Microarray analysis
PPI network
Signaling pathways
miRNA and lncRNA
title From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
title_full From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
title_fullStr From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
title_full_unstemmed From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
title_short From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells
title_sort from unipotency to pluripotency deciphering protein networks and signaling pathways in the generation of embryonic stem like cells from murine spermatogonial stem cells
topic Spermatogonial stem cells
Embryonic stem-like cells
Microarray analysis
PPI network
Signaling pathways
miRNA and lncRNA
url https://doi.org/10.1186/s12864-025-11612-y
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