A multidimensional atlas of human glioblastoma-like organoids reveals highly coordinated molecular networks and effective drugs

doi:10.1038/s41698-024-00500-5

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	A multidimensional atlas of human glioblastoma-like organoids reveals highly coordinated molecular networks and effective drugs
	Wang, Changwen 1,2,3; Sun, Meng4,5 ; Shao, Chunxuan 1; Schlicker, Lisa 6,7; Zhuo, Yue 1,8; Harim, Yassin 1,8; Peng, Tianping4,5 ; Tian, Weili 1; Stoeffler, Nadja 1; Schneider, Martin 7; Helm, Dominic 7; Chu, Youjun4 ; Fu, Beibei4,5 ; Jin, Xiaoliang 9,10; Mallm, Jan-Philipp 11; Mall, Moritz 12,13,14,15; Wu, Yonghe4 ; Schulze, Almut 6; Liu, Hai-Kun1,4
	2024-01-26
发表期刊	NPJ PRECISION ONCOLOGY
ISSN	2397-768X 01
EISSN	2397-768X
卷号	8 期号:1
发表状态	已发表
DOI	10.1038/s41698-024-00500-5
摘要	Recent advances in the genomics of glioblastoma (GBM) led to the introduction of molecular neuropathology but failed to translate into treatment improvement. This is largely attributed to the genetic and phenotypic heterogeneity of GBM, which are considered the major obstacle to GBM therapy. Here, we use advanced human GBM-like organoid (LEGO: Laboratory Engineered Glioblastoma-like Organoid) models and provide an unprecedented comprehensive characterization of LEGO models using single-cell transcriptome, DNA methylome, metabolome, lipidome, proteome, and phospho-proteome analysis. We discovered that genetic heterogeneity dictates functional heterogeneity across molecular layers and demonstrates that NF1 mutation drives mesenchymal signature. Most importantly, we found that glycerol lipid reprogramming is a hallmark of GBM, and several targets and drugs were discovered along this line. We also provide a genotype-based drug reference map using LEGO-based drug screen. This study provides new human GBM models and a research path toward effective GBM therapy.
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收录类别	SCI
语种	英语
资助项目	Deutsche Forschungsgemeinschaft[SFB1389] ; Deutsche Krebshilfe[110227] ; European Research Council (ERC)[647055] ; Deutschen Konsortium fur Translationale Krebsforschung (DKTK)[AIM2GO]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:001148743300001
出版者	NATURE PORTFOLIO
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349919
专题	免疫化学研究所生命科学与技术学院生命科学与技术学院_硕士生生命科学与技术学院_博士生免疫化学研究所_特聘教授组_刘海坤组
共同第一作者	Sun, Meng
通讯作者	Wang, Changwen; Liu, Hai-Kun
作者单位	1.German Canc Res Ctr, Div Mol Neurogenet, DKFZ ZMBH alliance, Neuenheimer Feld 581, D-69120 Heidelberg, Germany 2.Heidelberg Univ, Fac Med, Neuenheimer Feld 672, D-69120 Heidelberg, Germany 3.Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Thyroid Surg, Hangzhou 310003, Peoples R China 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.German Canc Res Ctr, Div Tumor Metab & Microenvironm, Neuenheimer Feld 581, D-69120 Heidelberg, Germany 7.German Canc Res Ctr, Prote Core Facil, Neuenheimer Feld 580, D-69120 Heidelberg, Germany 8.Heidelberg Univ, Fac Biosci, Neuenheimer Feld 234, D-69120 Heidelberg, Germany 9.Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Ophthalmol, Sch Med, Shanghai 200025, Peoples R China 10.Shanghai Key Lab Orbital Dis & Ocular Oncol, Shanghai 200025, Peoples R China 11.German Canc Res Ctr, Single cell Open Lab, Neuenheimer Feld 280, D-69120 Heidelberg, Germany 12.German Canc Res Ctr, Cell Fate Engn & Dis Modeling Grp, D-69120 Heidelberg, Germany 13.DKFZ ZMBH Alliance, D-69120 Heidelberg, Germany 14.HITBR Hector Inst Translat Brain Res gGmbH, D-69120 Heidelberg, Germany 15.Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, D-68159 Mannheim, Germany
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Wang, Changwen,Sun, Meng,Shao, Chunxuan,et al. A multidimensional atlas of human glioblastoma-like organoids reveals highly coordinated molecular networks and effective drugs[J]. NPJ PRECISION ONCOLOGY,2024,8(1).
APA	Wang, Changwen.,Sun, Meng.,Shao, Chunxuan.,Schlicker, Lisa.,Zhuo, Yue.,...&Liu, Hai-Kun.(2024).A multidimensional atlas of human glioblastoma-like organoids reveals highly coordinated molecular networks and effective drugs.NPJ PRECISION ONCOLOGY,8(1).
MLA	Wang, Changwen,et al."A multidimensional atlas of human glioblastoma-like organoids reveals highly coordinated molecular networks and effective drugs".NPJ PRECISION ONCOLOGY 8.1(2024).