Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes.
Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes.
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DOI：
10.1038/s41467-021-22331-9
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发表时间：
2021-04-09
影响因子：
16.6
通讯作者：
Patrakka J
中科院分区：
文献类型：
--
作者：
He B;Chen P;Zambrano S;Dabaghie D;Hu Y;Möller-Hackbarth K;Unnersjö-Jess D;Korkut GG;Charrin E;Jeansson M;Bintanel-Morcillo M;Witasp A;Wennberg L;Wernerson A;Schermer B;Benzing T;Ernfors P;Betsholtz C;Lal M;Sandberg R;Patrakka J
人类肾脏中单个细胞类型的分子表征以及模式生物对于定义器官功能和理解生物医学研究的转化方面至关重要。先前的研究已经揭示了几种肾小球细胞类型的基因表达谱，然而，包括系膜细胞（MCs）和肾小球壁上皮细胞（PECs）在内的重要细胞缺失或描述不完整，并且缺乏小鼠和人类肾脏之间的系统比较。为此，我们使用Smart-seq2分析了从人类活体供体肾脏活检和小鼠肾脏中分离的4332个肾小球相关细胞。该分析揭示了所有四种肾小球细胞类型（足细胞、肾小球内皮细胞、MCs和PECs）以及罕见的肾小球相关黄斑致密细胞的遗传程序。重要的是，我们检测了肾小球相关的pdgfrb表达细胞的异质性，包括具有功能活跃的吞噬分子机制的真正的肾小球内MCs，以及位于肾小球丛中央茎区独特的壁细胞类型。此外，我们观察到特定肾小球细胞类型的个体基因表达谱存在显著的物种差异，这突出了该领域的翻译挑战，并为设计翻译研究提供了指导。肾小球细胞的分子特性尚不清楚，啮齿类动物肾小球病变模型对人类的翻译效果也很差。在这里，作者利用单细胞RNA测序展示了肾小球相关细胞的分子特征，并强调了小鼠和人类细胞之间的差异。
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.
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影响因子：
13.6
作者：
Peti-Peterdi, Janos;Harris, Raymond C.
通讯作者：
Harris, Raymond C.
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
64.8
作者：
Hovestadt, Volker;Smith, Kyle S.;Northcott, Paul A.
通讯作者：
Northcott, Paul A.
影响因子：
48
作者：
Browaeys, Robin;Saelens, Wouter;Saeys, Yvan
通讯作者：
Saeys, Yvan
影响因子：
5.2
作者：
Lal MA;Patrakka J
通讯作者：
Patrakka J