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

doi:10.1084/jem.20202350

	Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse
	Guo, Duancheng 1,2; Wang, Yuan 2; Cheng, Yan 1; Liao, Shengyou 5; Hu, Jian 1; Du, Fang 1; Xu, Gang 1; Liu, Yongqiang 1; Cai, Kathy Q.1; Cheung, Martin 3; Wainwright, Brandon J.4; Lu, Q. Richard 6; Zhao, Yi 5; Yang, Zeng-jie 1
	2021-09-06
发表期刊	JOURNAL OF EXPERIMENTAL MEDICINE
ISSN	0022-1007
卷号	218 期号:9 页码:22
摘要	Astrocytes, 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.
DOI	10.1084/jem.20202350
收录类别	SCI
语种	英语
资助项目	American Cancer Society[RSG1605301NEC] ; American Brain Tumor Association[DG1900025] ; Pennsylvania CURE Health Research Fund[CURE 4100068716]
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:000701689900008
出版者	ROCKEFELLER UNIV PRESS
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/17063
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Zhao, Yi; Yang, Zeng-jie
作者单位	1.Temple Univ Hlth Syst, Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19140 USA 2.Soochow Univ, Coll Pharmaceut Sci, Pediat Canc Ctr, Suzhou, Peoples R China 3.Univ Hong Kong, Sch Biomed Sci, Li Ka Shing Fac Med, Hong Kong, Peoples R China 4.Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia 5.Chinese Acad Sci, Inst Comp Technol, Adv Comp Res Ctr, Key Lab Intelligent Informat Proc, Beijing, Peoples R China 6.Cincinnati Childrens Hosp Med Ctr, Brain Tumor Ctr, Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA
推荐引用方式 GB/T 7714	Guo, Duancheng,Wang, Yuan,Cheng, Yan,et al. Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2021,218(9):22.
APA	Guo, Duancheng.,Wang, Yuan.,Cheng, Yan.,Liao, Shengyou.,Hu, Jian.,...&Yang, Zeng-jie.(2021).Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse.JOURNAL OF EXPERIMENTAL MEDICINE,218(9),22.
MLA	Guo, Duancheng,et al."Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse".JOURNAL OF EXPERIMENTAL MEDICINE 218.9(2021):22.