Mass cytometry and transcriptomic profiling reveal body-wide pathology induced by Loxl1 deficiency.
Mass cytometry and transcriptomic profiling reveal body-wide pathology induced by Loxl1 deficiency.
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质谱流式分析和转录组分析揭示了 Loxl1 缺陷引起的全身病理学
DOI：
10.1111/cpr.13077
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发表时间：
2021-07
影响因子：
8.5
通讯作者：
Zou X
中科院分区：
文献类型：
--
作者：
Li Y;Wu B;An C;Jiang D;Gong L;Liu Y;Liu Y;Li J;Ouyang H;Zou X
据报道，LOXL1的表达缺失会导致盆腔器官脱垂或剥脱综合征青光眼。越来越多的证据表明，LOXL1缺乏与其他几种疾病的发病机制有关。然而，由于缺乏相关的研究技术，对LOXL1系统功能的表征受到限制。为了确定LOXL1的功能，建立了一种结合单细胞质量细胞术的全身器官转录组图谱的新方法。通过对Loxl1基因敲除(KO)小鼠和野生型小鼠17个器官组织的RNA-Seq测序，建立了全身器官转录(BOT)图谱。BOT结果表明，KO小鼠多个组织中与免疫反应和增殖过程相关的编码蛋白的基因全身性上调，组织学和免疫染色证实了KO小鼠组织中局部免疫细胞的增殖和渗透。此外，外周血样本的质量细胞仪分析显示了KO小鼠的全身免疫变化。这些发现与癌症数据库的结果有很好的相关性。肿瘤患者的Loxl1突变频率较高，Loxl1突变的肿瘤患者表现出免疫过程和细胞增殖上调，存活率较低。本研究为多器官基因功能的筛选提供了一种有效的策略，并阐明了LOXL1在多器官细胞和系统免疫中的重要生物学作用。建立了一种新的全身器官转录组谱分析方法，结合单细胞质量细胞术对Loxl1基因敲除小鼠和野生型(WT)小鼠的17个器官进行了RNA序列分析，揭示了Loxl1缺乏引起的全身病变(包括免疫细胞的增殖和渗透)，为筛选特定基因的全身器官功能提供了有力的策略，并阐明了LOXL1在多器官细胞和系统免疫中的重要生物学作用。
The loss of LOXL1 expression reportedly leads to the prolapse of pelvic organs or to exfoliation syndrome glaucoma. Increasing evidence suggests that LOXL1 deficiency is associated with the pathogenesis of several other diseases. However, the characterization of the systemic functions of LOXL1 is limited by the lack of relevant investigative technologies. To determine the functions of LOXL1, a novel method for body‐wide organ transcriptome profiling, combined with single‐cell mass cytometry, was developed. A body‐wide organ transcriptomic (BOT) map was created by RNA‐Seq of tissues from 17 organs from both Loxl1 knockout (KO) and wild‐type mice. The BOT results indicated the systemic upregulation of genes encoding proteins associated with the immune response and proliferation processes in multiple tissues of KO mice, and histological and immune staining confirmed the hyperplasia and infiltration of local immune cells in the tissues of KO mice. Furthermore, mass cytometry analysis of peripheral blood samples revealed systemic immune changes in KO mice. These findings were well correlated with results obtained from cancer databases. Patients with tumours had higher Loxl1 mutation frequencies, and patients with Loxl1‐mutant tumours showed the upregulation of immune processes and cell proliferation and lower survival rates. This study provides an effective strategy for the screening of gene functions in multiple organs and also illustrates the important biological roles of LOXL1 in the cells of multiple organs as well as in systemic immunity. A new method for body‐wide organ transcriptome profiling, combined with single‐cell mass cytometry was developed to perform RNA‐seq of 17 organs from both Loxl1 knockout and wide type (WT) mice reveal body wide pathology (including hyperplasia and infiltration of immune cells) induced by Loxl1 deficiency, which provided a powerful strategy to screen body‐wide organ functions of a particular gene, and also illustrated important biological roles of LOXL1 on multiple organ cells and systemic immunity.
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影响因子：
4
作者：
Proserpio V;Lönnberg T
通讯作者：
Lönnberg T
影响因子：
16.6
作者：
Nakasaki M;Hwang Y;Xie Y;Kataria S;Gund R;Hajam EY;Samuel R;George R;Danda D;M J P;Nakamura T;Shen Z;Briggs S;Varghese S;Jamora C
通讯作者：
Jamora C
影响因子：
16.6
作者：
Mammoto, Akiko;Mammoto, Tadanori;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
6
作者：
Drewes, Peter G.;Yanagisawa, Hiromi;Word, R. Ann
通讯作者：
Word, R. Ann
LOXL1通过抑制YAP转录活性调节结直肠癌的恶性进展
影响因子：
8.4
作者：
Hu, Lin;Wang, Jing;Chin, Y. Eugene
通讯作者：
Chin, Y. Eugene