Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair

Abstract Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant‐derived compounds are screened for in v...

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Main Authors: Chunlan Mu, Xiaoyong Li, Jiamei Yang, Geng G. Tian, Hepeng Bai, Wenhui Lin, Linhui Wang, Ji Wu
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202410098
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author Chunlan Mu
Xiaoyong Li
Jiamei Yang
Geng G. Tian
Hepeng Bai
Wenhui Lin
Linhui Wang
Ji Wu
author_facet Chunlan Mu
Xiaoyong Li
Jiamei Yang
Geng G. Tian
Hepeng Bai
Wenhui Lin
Linhui Wang
Ji Wu
author_sort Chunlan Mu
collection DOAJ
description Abstract Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant‐derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder‐free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo‐time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A‐Eph receptor B2 ligand‐receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant‐derived compounds.
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institution Kabale University
issn 2198-3844
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publisher Wiley
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series Advanced Science
spelling doaj-art-2529cef0a6c143aaa39aa83e9e274c172025-01-29T09:50:19ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202410098Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 PairChunlan Mu0Xiaoyong Li1Jiamei Yang2Geng G. Tian3Hepeng Bai4Wenhui Lin5Linhui Wang6Ji Wu7School of Basic Medical Sciences Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education Ningxia Medical University Yinchuan 750004 ChinaKey Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education) Bio‐X Institutes Shanghai Jiao Tong University Shanghai 200240 ChinaSchool of Basic Medical Sciences Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education Ningxia Medical University Yinchuan 750004 ChinaSchool of Agriculture and Biology Shanghai Jiao Tong University Shanghai 200240 ChinaKey Laboratory for the Genetics of Developmental & Neuropsychiatric Disorders (Ministry of Education) Bio‐X Institutes Shanghai Jiao Tong University Shanghai 200240 ChinaSchool of Life Sciences and Biotechnology Joint International Research Laboratory of Metabolic and Developmental Sciences Shanghai Jiao Tong University Shanghai 200240 ChinaDepartment of Urology, Changhai Hospital Second Military Medical University (Naval Medical University) Shanghai 200433 ChinaSchool of Basic Medical Sciences Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education Ningxia Medical University Yinchuan 750004 ChinaAbstract Ovarian dysfunction is a major factor leading to female infertility. Understanding how to improve or reshape ovarian function has become an important entry point for preventing and treating female infertility caused by ovarian dysfunction. Here, plant‐derived compounds are screened for in vitro activity upon ovarian organoids derived from feeder‐free female germline stem cells. Tetrahydroxy stilbene glucoside (TSG) is found to promote the development of ovarian organoids. Single nucleus transcriptome sequencing and spatial transcriptome sequencing are used to establish a comprehensive spatiotemporal map to elucidate the role of TSG in ovarian organoid development, encompassing cell types and subtypes, transcription factors, pseudo‐time sequence, and cell communication dynamics. This analysis indicates that TSG promotes ovarian organoid development through the vascular endothelial growth factor A‐Eph receptor B2 ligand‐receptor pair between granulosa cells and oocytes. This study has enhanced the understanding of the mechanisms of ovarian organoid development, establishes a technical platform for screening compounds for treating infertility and related diseases, and lays a foundation for clinically applying plant‐derived compounds.https://doi.org/10.1002/advs.202410098ligand‐receptor pairsovarian organoidsplant‐derived compoundssingle nucleus transcriptome sequencingspatial transcriptome sequencing
spellingShingle Chunlan Mu
Xiaoyong Li
Jiamei Yang
Geng G. Tian
Hepeng Bai
Wenhui Lin
Linhui Wang
Ji Wu
Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
Advanced Science
ligand‐receptor pairs
ovarian organoids
plant‐derived compounds
single nucleus transcriptome sequencing
spatial transcriptome sequencing
title Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
title_full Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
title_fullStr Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
title_full_unstemmed Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
title_short Spatial Transcriptome and Single Nucleus Transcriptome Sequencing Reveals Tetrahydroxy Stilbene Glucoside Promotes Ovarian Organoids Development Through the Vegfa‐Ephb2 Pair
title_sort spatial transcriptome and single nucleus transcriptome sequencing reveals tetrahydroxy stilbene glucoside promotes ovarian organoids development through the vegfa ephb2 pair
topic ligand‐receptor pairs
ovarian organoids
plant‐derived compounds
single nucleus transcriptome sequencing
spatial transcriptome sequencing
url https://doi.org/10.1002/advs.202410098
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