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Article: Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse

TitleTumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse
Authors
Issue Date2021
PublisherRockefeller University Press. The Journal's web site is located at http://www.jem.org
Citation
The Journal of Experimental Medicine, 2021, v. 218 n. 9, p. article no. e20202350 How to Cite?
AbstractAstrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation. © 2021 Guo et al.
DescriptionHybrid open access
Persistent Identifierhttp://hdl.handle.net/10722/301160
ISSN
2023 Impact Factor: 12.6
2023 SCImago Journal Rankings: 6.838
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGuo, D-
dc.contributor.authorWang, Y-
dc.contributor.authorCheng, Y-
dc.contributor.authorLiao, S-
dc.contributor.authorHu, J-
dc.contributor.authorDu, F-
dc.contributor.authorXu, GANG-
dc.contributor.authorLiu, Y-
dc.contributor.authorCai, KQ-
dc.contributor.authorCheung, M-
dc.contributor.authorWainwright, BJ-
dc.contributor.authorLu, QR-
dc.contributor.authorZhao, YI-
dc.contributor.authorYang, ZJ-
dc.date.accessioned2021-07-27T08:07:01Z-
dc.date.available2021-07-27T08:07:01Z-
dc.date.issued2021-
dc.identifier.citationThe Journal of Experimental Medicine, 2021, v. 218 n. 9, p. article no. e20202350-
dc.identifier.issn0022-1007-
dc.identifier.urihttp://hdl.handle.net/10722/301160-
dc.descriptionHybrid open access-
dc.description.abstractAstrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation. © 2021 Guo et al.-
dc.languageeng-
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jem.org-
dc.relation.ispartofThe Journal of Experimental Medicine-
dc.rightsThe Journal of Experimental Medicine. Copyright © Rockefeller University Press.-
dc.rights©2021 Guo D.,Wang Y. and Cheng Y. ... et al. Originally published in The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20202350-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleTumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse-
dc.typeArticle-
dc.identifier.emailCheung, M: mcheung9@hku.hk-
dc.identifier.authorityCheung, M=rp00245-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1084/jem.20202350-
dc.identifier.scopuseid_2-s2.0-85110562781-
dc.identifier.hkuros323650-
dc.identifier.volume218-
dc.identifier.issue9-
dc.identifier.spagearticle no. e20202350-
dc.identifier.epagearticle no. e20202350-
dc.identifier.isiWOS:000701689900008-
dc.publisher.placeUnited States-

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