Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma.
Multimodal single-cell analysis reveals distinct radioresistant stem-like and progenitor cell populations in murine glioma.
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作者：
Alexander J;LaPlant QC;Pattwell SS;Szulzewsky F;Cimino PJ;Caruso FP;Pugliese P;Chen Z;Chardon F;Hill AJ;Spurrell C;Ahrendsen D;Pietras A;Starita LM;Hambardzumyan D;Iavarone A;Shendure J;Holland EC
放射治疗是神经胶质瘤标准治疗的一部分，可以杀死一部分肿瘤细胞，同时改变肿瘤微环境。具有干细胞样特性的肿瘤细胞优先在辐射中存活并引起胶质瘤复发。已经使用了用于富集和定量具有干细胞样特性的细胞的各种技术，包括基于荧光激活细胞分选（FACS）的侧群（SP）测定，这是一种富集干细胞样肿瘤细胞的功能测定。在这些分析中，胶质瘤的小鼠模型已被用于了解这种疾病的生物学和治疗反应，包括辐射反应。我们提出了神经胶质瘤基因工程小鼠模型的联合SP分析和单细胞RNA测序，以显示细胞对辐射反应的时间过程。我们确定并表征了两种不同的肿瘤细胞群体，它们具有固有的放射抗性，并且放射对肿瘤微环境中的免疫细胞群体也具有不同的影响。在照射小鼠神经胶质瘤后早期，FACS分析显示干细胞样细胞富集，scRNA-seq显示放射抗性肿瘤细胞是祖细胞和干细胞样细胞。此外，小胶质细胞和巨噬细胞群体发生变化。
Radiation therapy is part of the standard of care for gliomas and kills a subset of tumor cells, while also altering the tumor microenvironment. Tumor cells with stem‐like properties preferentially survive radiation and give rise to glioma recurrence. Various techniques for enriching and quantifying cells with stem‐like properties have been used, including the fluorescence activated cell sorting (FACS)‐based side population (SP) assay, which is a functional assay that enriches for stem‐like tumor cells. In these analyses, mouse models of glioma have been used to understand the biology of this disease and therapeutic responses, including the radiation response. We present combined SP analysis and single‐cell RNA sequencing of genetically‐engineered mouse models of glioma to show a time course of cellular response to radiation. We identify and characterize two distinct tumor cell populations that are inherently radioresistant and also distinct effects of radiation on immune cell populations within the tumor microenvironment. Early after irradiation of murine glioma, FACS‐analysis shows stem‐like cells are enriched, and scRNA‐seq shows the radioresistant tumor cells are progenitors and stem‐like cells. Also, microglia and macrophage populations shift.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
FGFR3-TACC3 基因融合体在癌症中的代谢功能。
影响因子：
64.8
作者：
Frattini V;Pagnotta SM;Tala;Fan JJ;Russo MV;Lee SB;Garofano L;Zhang J;Shi P;Lewis G;Sanson H;Frederick V;Castano AM;Cerulo L;Rolland DCM;Mall R;Mokhtari K;Elenitoba-Johnson KSJ;Sanson M;Huang X;Ceccarelli M;Lasorella A;Iavarone A
通讯作者：
Iavarone A
影响因子：
50.3
作者：
Fedele, Monica;Visone, Rosa;Fusco, Alfredo
通讯作者：
Fusco, Alfredo
影响因子：
3.7
作者：
Fomchenko EI;Dougherty JD;Helmy KY;Katz AM;Pietras A;Brennan C;Huse JT;Milosevic A;Holland EC
通讯作者：
Holland EC
影响因子：
64.5
作者：
Ceccarelli M;Barthel FP;Malta TM;Sabedot TS;Salama SR;Murray BA;Morozova O;Newton Y;Radenbaugh A;Pagnotta SM;Anjum S;Wang J;Manyam G;Zoppoli P;Ling S;Rao AA;Grifford M;Cherniack AD;Zhang H;Poisson L;Carlotti CG Jr;Tirapelli DP;Rao A;Mikkelsen T;Lau CC;Yung WK;Rabadan R;Huse J;Brat DJ;Lehman NL;Barnholtz-Sloan JS;Zheng S;Hess K;Rao G;Meyerson M;Beroukhim R;Cooper L;Akbani R;Wrensch M;Haussler D;Aldape KD;Laird PW;Gutmann DH;TCGA Research Network;Noushmehr H;Iavarone A;Verhaak RG
通讯作者：
Verhaak RG