Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma.
Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma.
复制标题
DOI：
10.1016/j.celrep.2022.111743
复制
发表时间：
2022-11-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
涎腺样囊性癌（ACC）是一种罕见的，生物学上独特的双相肿瘤，由恶性肌上皮细胞和腔细胞组成。MYB和Notch信号与ACC病理生理有关，但在人类肿瘤中对这两个程序的体内描述和对它们的主动协调的研究仍然不完整。我们利用单细胞RNA测序来分析人类头颈部ACC，包括原发性ACC与匹配的局部复发的比较。我们定义了这些罕见肿瘤的表达异质性，揭示了肌上皮细胞和管腔细胞表达的多样性。我们发现Notch配体DLL1、JAG1和JAG2在肌上皮细胞中的差异表达，表明旁分泌相互作用可能支持致癌Notch信号传导。我们在三个已发表的ACC患者队列中验证了这种选择性表达。我们的数据为中低级别ACC的双期性提供了一种潜在的解释，并可能有助于指导针对这些肿瘤的新治疗策略。Parikh等人利用单细胞RNA-seq技术对腺样囊性癌（adenoid cystic carcinoma， ACC）的恶性细胞和间质细胞进行了表征。肌上皮细胞表达Notch配体，而管腔细胞显示Notch信号，这与ACC的旁分泌机制和双相性一致。复发性ACC多管状，Notch信号增加。
Salivary adenoid cystic carcinoma (ACC) is a rare, biologically unique biphasic tumor that consists of malignant myoepithelial and luminal cells. MYB and Notch signaling have been implicated in ACC pathophysiology, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilize single-cell RNA sequencing to profile human head and neck ACC, including a comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering diversity in myoepithelial and luminal cell expression. We find differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We validate this selective expression in three published cohorts of patients with ACC. Our data provide a potential explanation for the biphasic nature of low- and intermediate-grade ACC and may help direct new therapeutic strategies against these tumors. Parikh et al. use single-cell RNA-seq to characterize the malignant and stromal cells in adenoid cystic carcinoma (ACC). Myoepithelial cells express Notch ligands, while luminal cells show Notch signaling, consistent with a paracrine mechanism and the biphasic nature of ACC. Recurrent ACC is more luminal, with increased Notch signaling.
登录
查看更多内容
影响因子：
30.8
作者：
Ho, Allen S.;Kannan, Kasthuri;Roy, David M.;Morris, Luc G. T.;Ganly, Ian;Katabi, Nora;Ramaswami, Deepa;Walsh, Logan A.;Eng, Stephanie;Huse, Jason T.;Zhang, Jianan;Dolgalev, Igor;Huberman, Kety;Heguy, Adriana;Viale, Agnes;Drobnjak, Marija;Leversha, Margaret A.;Rice, Christine E.;Singh, Bhuvanesh;Iyer, N. Gopalakrishna;Leemans, C. Rene;Bloemena, Elisabeth;Ferris, Robert L.;Seethala, Raja R.;Gross, Benjamin E.;Liang, Yupu;Sinha, Rileen;Peng, Luke;Raphael, Benjamin J.;Turcan, Sevin;Gong, Yongxing;Schultz, Nikolaus;Kim, Seungwon;Chiosea, Simion;Shah, Jatin P.;Sander, Chris;Lee, William;Chan, Timothy A.
通讯作者：
Chan, Timothy A.
影响因子：
16.6
作者：
Karaayvaz M;Cristea S;Gillespie SM;Patel AP;Mylvaganam R;Luo CC;Specht MC;Bernstein BE;Michor F;Ellisen LW
通讯作者：
Ellisen LW
影响因子：
15.9
作者：
Ho, Allen S.;Ochoa, Angelica;Morris, Luc G. T.
通讯作者：
Morris, Luc G. T.
影响因子：
2.1
作者：
Barrera, Jose E.;Shroyer, Kenneth R.;Greer, Robert O.
通讯作者：
Greer, Robert O.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK