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
中科院分区:
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
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.
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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
通讯作者:
Skaer H
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
影响因子:
4.6
作者:
Caubit, Xavier;Lye, Claire M.;Fasano, Laurent
通讯作者:
Fasano, Laurent
影响因子:
9.2
作者:
Denholm, B;Sudarsan, V;Skaer, H
通讯作者:
Skaer, H