Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH..
High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1+ ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1+ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1+ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 10(2023), 15 vom: 24. Mai, Seite e2205525 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Meng [VerfasserIn] |
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| Links: |
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| Themen: |
Cell subpopulation |
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| Anmerkungen: |
Date Completed 29.05.2023 Date Revised 31.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/advs.202205525 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354996029 |
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| 520 | |a © 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. | ||
| 520 | |a High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1+ ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1+ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1+ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a cell subpopulation | |
| 650 | 4 | |a meningioma | |
| 650 | 4 | |a patient-derived organoid model | |
| 650 | 4 | |a single-cell RNA sequencing | |
| 700 | 1 | |a Xu, Shao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuzhe |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Zhan, Xiudan |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Chaoyin |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zijin |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Lina |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Wenyong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qing |e verfasserin |4 aut | |
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