Transcriptional and functional motifs defining renal function revealed by single-nucleus RNA sequencing.

Transcriptional and functional motifs defining renal function revealed by single-nucleus RNA sequencing.
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DOI:
10.1073/pnas.2203179119
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发表时间:
2022-06-21
影响因子:
11.1
通讯作者:
Perrimon, Norbert
Perrimon, Norbert
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu, Jun;Liu, Yifang;Li, Hongjie;Tarashansky, Alexander J.;Kalicki, Colin H.;Hung, Ruei-Jiun;Hu, Yanhui;Comjean, Aram;Kolluru, Sai Saroja;Wang, Bo;Quake, Stephen R.;Luo, Liqun;McMahon, Andrew P.;Dow, Julian A. T.;Perrimon, Norbert

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我们进行了一个单核RNA测序研究的成年苍蝇肾,确定了11个不同的集群,我们验证了基因标记。我们描述了参与干细胞再生和代谢的转录因子的作用,以及调节星状细胞不寻常的细胞形状的基因。该数据集还提供了小管的组织和生理作用的系统级视图。最后,我们进行了一个跨物种的分析,允许比较苍蝇肾细胞类型与小鼠肾细胞类型,以及涡虫原肾。本研究为昆虫肾脏的研究提供了一个全面的资源。单细胞测序的最新进展为获得对构成组织/器官的细胞类型的多样性、谱系和功能的新见解提供了独特的机会。在这里,我们进行了单核研究的成年果蝇肾脏系统,包括马氏管和肾细胞,这与哺乳动物的肾脏相似。我们确定了11个不同的集群代表肾干细胞,星状细胞,区域特异性主细胞,加兰肾细胞,心包肾细胞。对每个簇特异性转录因子的表征确定了fruitless(fru)在干细胞再生中发挥作用,以及肝细胞核因子4(Hnf 4)在调节糖原和甘油三酯代谢中发挥作用。此外,我们确定了一些基因,包括Rho鸟嘌呤核苷酸交换因子64 C(RhoGEF 64 c),Frequenin 2(Frq 2),Prip和CG 1093,参与调节星状细胞的不寻常的星星形状。重要的是,单核数据集允许可视化参与离子转运和连接通透性的基因在器官水平的表达,提供了小管组织和生理作用的系统水平视图。最后,跨物种分析使我们能够将苍蝇肾细胞类型与小鼠肾细胞类型和Planarian原肾管相匹配,这些知识将有助于肾脏疾病模型的生成。总之,我们的研究提供了一个全面的资源,研究苍蝇肾。
We performed a single-nucleus RNA sequencing study of the adult fly kidney, identifying 11 distinct clusters that we validated by gene markers. We characterized the roles of transcription factors involved in stem cell regeneration and metabolism, as well as genes that regulate the unusual cell shape of stellate cells. The dataset also provides a systems-level view of the organization and physiological roles of the tubules. Finally, we performed a cross-species analysis that allowed a comparison of the fly kidney cell types with mouse kidney cell types, as well as planarian protonephridia. This study provides a comprehensive resource for studying the insect kidney. Recent advances in single-cell sequencing provide a unique opportunity to gain novel insights into the diversity, lineage, and functions of cell types constituting a tissue/organ. Here, we performed a single-nucleus study of the adult Drosophila renal system, consisting of Malpighian tubules and nephrocytes, which shares similarities with the mammalian kidney. We identified 11 distinct clusters representing renal stem cells, stellate cells, regionally specific principal cells, garland nephrocyte cells, and pericardial nephrocytes. Characterization of the transcription factors specific to each cluster identified fruitless (fru) as playing a role in stem cell regeneration and Hepatocyte nuclear factor 4 (Hnf4) in regulating glycogen and triglyceride metabolism. In addition, we identified a number of genes, including Rho guanine nucleotide exchange factor at 64C (RhoGEF64c), Frequenin 2 (Frq2), Prip, and CG1093 that are involved in regulating the unusual star shape of stellate cells. Importantly, the single-nucleus dataset allows visualization of the expression at the organ level of genes involved in ion transport and junctional permeability, providing a systems-level view of the organization and physiological roles of the tubules. Finally, a cross-species analysis allowed us to match the fly kidney cell types to mouse kidney cell types and planarian protonephridia, knowledge that will help the generation of kidney disease models. Altogether, our study provides a comprehensive resource for studying the fly kidney.
DOI: 10.1242/dev.088989
发表时间: 2013-03
期刊: Development (Cambridge, England)
影响因子: --
作者:
Denholm B;Hu N;Fauquier T;Caubit X;Fasano L;Skaer H
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DOI: 10.1098/rspb.2012.2943
发表时间: 2013-04-22
期刊: Proceedings. Biological sciences
影响因子: --
作者:
Cabrero P;Richmond L;Nitabach M;Davies SA;Dow JA
通讯作者: Dow JA
DOI: 10.26355/eurrev_202006_21542
发表时间: 2020-06-01
影响因子: 3.3
作者:
Fan, Q-X;Gong, S-Q;Zhang, F-J
通讯作者: Zhang, F-J
DOI: 10.1242/dev.022442
发表时间: 2008-10-01
期刊: DEVELOPMENT
影响因子: 4.6
作者:
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通讯作者: Fasano, Laurent
DOI: 10.1016/s0960-9822(03)00375-0
发表时间: 2003-06-17
期刊: CURRENT BIOLOGY
影响因子: 9.2
作者:
Denholm, B;Sudarsan, V;Skaer, H
通讯作者: Skaer, H