Xu, J. et al. (2022) Transcriptional and functional motifs defining renal function revealed by single-nucleus RNA sequencing. Proceedings of the National Academy of Sciences of the United States of America, 119(25), e220317911. (doi: 10.1073/pnas.2203179119) (PMID:35696569) (PMCID:PMC9231607)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Additional Information: | Relevant grants support include NIA R00 AG062746 (H.L.), NIDCD R01 DC005982 566 (LL), NIDDK (DK107350, DK094526, DK110792) (A.P.M.), and BBSRC-NSF (NP). H.L. is a CPRIT scholar. S.R.Q. is an investigator of Chan Zuckerberg Biohub. J.A.T.D. is supported by UK BBSRC grants BB/P024297/1 and BB/V011154/1. L.L. and N.P. are investigators of Howard Hughes Medical Institute. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Dow, Professor Julian |
| Authors: | Xu, J., Liu, Y., Lib, H., Tarashansky, A. J., Kalicki, C. H., Hung, R.-J., Hua, Y., Comjean, A., Kolluru, S. S., Wang, B., Quake, S. R., Luo, L., McMahon, A. P., Dow, J. A.T., and Perrimon, N. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 13 June 2022 |
| Copyright Holders: | Copyright © 2022 the Author(s) |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 119(25): e220317911 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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