He, Bing ORCID: 0000-0003-3877-4872, Chen, Ping ORCID: 0000-0002-8068-1891, Zambrano, Sonia, Dabaghie, Dina, Hu, Yizhou ORCID: 0000-0002-2635-0258, Moller-Hackbarth, Katja, Unnersjoe-Jess, David, Korkut, Gul Gizem, Charrin, Emmanuelle ORCID: 0000-0001-6043-858X, Jeansson, Marie, Bintanel-Morcillo, Maria, Witasp, Anna, Wennberg, Lars, Wernerson, Annika, Schermer, Bernhard, Benzing, Thomas, Ernfors, Patrik, Betsholtz, Christer, Lal, Mark, Sandberg, Rickard and Patrakka, Jaakko (2021). Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes. Nat. Commun., 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies. The molecular identity of renal glomerular cells is poorly characterized and rodent glomerulopathy models translate poorly to humans. Here, the authors show molecular signatures of glomerulus-associated cells using single cell RNA sequencing and highlight differences between mouse and human cells.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
He, BingUNSPECIFIEDorcid.org/0000-0003-3877-4872UNSPECIFIED
Chen, PingUNSPECIFIEDorcid.org/0000-0002-8068-1891UNSPECIFIED
Zambrano, SoniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dabaghie, DinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, YizhouUNSPECIFIEDorcid.org/0000-0002-2635-0258UNSPECIFIED
Moller-Hackbarth, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Unnersjoe-Jess, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korkut, Gul GizemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Charrin, EmmanuelleUNSPECIFIEDorcid.org/0000-0001-6043-858XUNSPECIFIED
Jeansson, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bintanel-Morcillo, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witasp, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wennberg, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wernerson, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ernfors, PatrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Betsholtz, ChristerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, MarkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandberg, RickardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patrakka, JaakkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-589932
DOI: 10.1038/s41467-021-22331-9
Journal or Publication Title: Nat. Commun.
Volume: 12
Number: 1
Date: 2021
Publisher: NATURE PORTFOLIO
Place of Publication: BERLIN
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
RENIN EXPRESSION; MOUSE; SEQ; ZONATION; TARGET; ALPHAMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58993

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