scholarly journals Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity

2021 ◽  
Author(s):  
Caitriona M McEvoy ◽  
Julia M Murphy ◽  
Lin Zhang ◽  
Sergi Clotet-Freixas ◽  
Jessica A Mathews ◽  
...  
Keyword(s):  
Single Cell ◽  
Human Kidney ◽  
Cell Types ◽  
Significant Heterogeneity ◽  
Proximal Tubular Cells ◽  
Healthy Human ◽  
Fresh Tissue ◽  
Tubular Cells ◽  
Distinct Cell ◽  
Proximal Tubular

Maintaining organ homeostasis requires complex functional synergy between distinct cell types, a snapshot of which is glimpsed through the simultaneously broad and granular analysis provided by single-cell atlases. Knowledge of the transcriptional programs underpinning the complex and specialized functions of human kidney cell populations at homeostasis is limited by difficulty accessing healthy, fresh tissue. Here, we present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed between male and female proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. Within the immune niche, we identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions and validated findings by flow cytometry. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations.

The Anti-Leu4 (CD3) Monoclonal Antibody Reacts with Proximal Tubular Cells of the Human Kidney

1989 ◽  
Vol 30 (6) ◽  
pp. 719-722 ◽  
Author(s):  
A. KARLSSON-PARRA ◽  
E. DIMENY ◽  
C. JUHLIN ◽  
B. FELLSTROM ◽  
L. KLARESKOG
Keyword(s):  
Monoclonal Antibody ◽  
Human Kidney ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

scholarly journals Structure–Interaction Relationship of Polymyxins with the Membrane of Human Kidney Proximal Tubular Cells

2020 ◽  
Vol 6 (8) ◽  
pp. 2110-2119 ◽  
Author(s):  
Xukai Jiang ◽  
Shuo Zhang ◽  
Mohammad A. K. Azad ◽  
Kade D. Roberts ◽  
Lin Wan ◽  
...  
Keyword(s):  
Human Kidney ◽  
Proximal Tubular Cells ◽  
Structure Interaction ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Kidney Proximal Tubular Cells ◽  
Relationship Of ◽  
Interaction Relationship

scholarly journals Effect of TIMP1 transfection on PTEN expression in human kidney proximal tubular cells

2015 ◽  
Vol 14 (4) ◽  
pp. 17373-17383 ◽  
Author(s):  
J.X. Chen ◽  
G.Y. Cai ◽  
X.M. Chen ◽  
H. Liu ◽  
X. Chen ◽  
...  
Keyword(s):  
Human Kidney ◽  
Pten Expression ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Kidney Proximal Tubular Cells

scholarly journals Costimulation with angiotensin II and interleukin 6 augments angiotensinogen expression in cultured human renal proximal tubular cells

2008 ◽  
Vol 295 (1) ◽  
pp. F283-F289 ◽  
Author(s):  
Ryousuke Satou ◽  
Romer A. Gonzalez-Villalobos ◽  
Kayoko Miyata ◽  
Naro Ohashi ◽  
Akemi Katsurada ◽  
...  
Keyword(s):  
Human Kidney ◽  
Ang Ii ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Human Renin ◽  
Protein Expressions ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

Augmented intrarenal ANG II stimulates IL-6, which contributes to renal injury. The expression of intrarenal angiotensinogen (AGT) is enhanced by increased intrarenal ANG II in human renin/human AGT double transgenic mice. ANG II also augments AGT expression in hepatocytes and cardiac myocytes. However, the mechanisms underlying AGT augmentation by ANG II and the contribution of IL-6 to this system are poorly understood. This study was performed in human renal proximal tubular epithelial cells (HRPTECs) to test the hypothesis that IL-6 contributes to the upregulation of AGT expression by ANG II. Human kidney-2 (HK-2) cells, immortalized HRPTECs, were incubated with 10−7 M ANG II and/or 10 ng/ml IL-6 for up to 24 h. AGT mRNA and protein expressions were measured by real-time RT-PCR and ELISA, respectively. The activities of NF-κB and STAT3 were evaluated by Western blotting and EMSA. Stimulation with either ANG II or IL-6 did not significantly alter AGT mRNA or protein expression. In contrast, costimulation with ANG II and IL-6 significantly increased AGT mRNA and protein expressions (1.26 ± 0.10 and 1.16 ± 0.13 over control, respectively). Olmesartan, an ANG II type 1 receptor blocker, and an IL-6 receptor antibody individually inhibited this synergistic effect. NF-κB was also activated by costimulation with ANG II and IL-6. Phosphorylation and activity of STAT3 were increased by stimulation with IL-6 alone and by costimulation. The present study indicates that IL-6 plays an important role in ANG II-mediated augmentation of AGT expression in human renal proximal tubular cells.

scholarly journals Angiotensin II as a renal growth factor.

1993 ◽  
Vol 3 (9) ◽  
pp. 1531-1540 ◽  
Author(s):  
G Wolf ◽  
E G Neilson
Keyword(s):  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Cell Types ◽  
Signal Transduction Pathways ◽  
Ang Ii ◽  
Proximal Tubular Cells ◽  
Renal Growth ◽  
Converting Enzyme Inhibitors ◽  
Tubular Cells ◽  
Proximal Tubular

Angiotensin II (ANG II) can have multiple effects on the kidney, including influences on the regulation of glomerular hemodynamics and tubular transport as well as consequences for the glomerular processing of macromolecules. The recognized suppressive effects of angiotensin-converting enzyme inhibitors on compensatory renal growth, even in the absence of hemodynamic effects, and the well-documented proliferative effect of ANG II on vascular smooth muscle cells have provided the background for the recent intensive interest in this peptide as a renal cytokine. Diverse cell types along the nephron express a variety of ANG II receptors. These receptors and their putative signal transduction pathways have been best characterized in mesangial and proximal tubular cells. Culture experiments provide convincing evidence that ANG II can be a phenotypic influence on these cell types. The growth responses and the associated signal transduction pathways, however, are different in mesangial and proximal tubular cells. These ANG II-mediated responses are also associated with an increase in the synthesis of distinct collagen subtypes, potentially linking the growth stimulatory effects of ANG II to the irreversible changes of glomerulosclerosis and tubulointerstitial fibrosis observed in chronic renal failure. Preventing the intrarenal actions of ANG II with angiotensin-converting enzyme inhibitors or with the new, orally active, selective ANG II receptor antagonists may provide a rational therapeutic approach to attenuate the progression of a variety of kidney diseases.

scholarly journals Novel Human Kidney Cell Subsets Identified by Mux-Seq

2020 ◽  
Author(s):  
Andrew W. Schroeder ◽  
Swastika Sur ◽  
Priyanka Rashmi ◽  
Izabella Damm ◽  
Arya Zarinsefat ◽  
...  
Keyword(s):  
Single Cell ◽  
Collecting Duct ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Cost Effective ◽  
Cell Types ◽  
Single Cell Rna Sequencing ◽  
Proximal Tubular ◽  
Highly Correlated ◽  
First Time

AbstractBackgroundThe kidney is a highly complex organ that performs multiple functions necessary to maintain systemic homeostasis, with complex interplay from different kidney sub-structures and the coordinated response of diverse cell types, few known and likely many others, as yet undiscovered. Traditional global sequencing techniques are limited in their ability to identify unique and functionally diverse cell types in complex tissues.MethodsHerein we characterize over 45,000 cells from 10 normal human kidneys using unbiased single-cell RNA sequencing. We also apply, for the first time, an approach of multiplexing kidney samples (Mux-Seq), pooled from different individuals, to save input sample amount and cost. We applied the computational tool Demuxlet to assess differential expression across multiple individuals by pooling human kidney cells for scRNA sequencing, utilizing individual genetic variability to determine the identity of each cell.ResultsMultiplexed droplet single-cell RNA sequencing results were highly correlated with the singleplexed sample run data. One hundred distinct cell cluster populations in total were identified across the major cell types of the kidney, with varied functional states. Proximal tubular and collecting duct cells were the most heterogeneous, displaying multiple clusters with unique ontologies. Novel proximal tubular cell subsets were identified with regenerative potential. Trajectory analysis demonstrated evolution of cell states between intercalated and principal cells in the collecting duct.ConclusionsHealthy kidney tissue has been successfully analyzed to detect all known renal cell types, inclusive of resident and infiltrating immune cells in the kidney. Mux-Seq is a unique method that allows for rapid and cost-effective single cell, in depth, transcriptional analysis of human kidney tissue.Significance StatementUse of renal biopsies for single cell transcriptomics is limited by small tissue availability and batch effects. In this study, we have successfully employed the use of Mux-Seq for the first time in kidney. Mux-Seq allows the use of single cell technology at a much more cost-effective manner by pooling samples from multiple individuals for a single sequencing run. This is even more relevant in the case of patient biopsies where the input of tissue is significantly limited. We show that the data from overlapping tissue samples are highly correlated between Mux-Seq and traditional Singleplexed RNA seq. Furthermore, the results from Mux-Seq of 4 pooled samples are highly correlated with singleplexed data from 10 singleplex samples despite the inherent variability among individuals.

Mitochondrial Inclusions

1968 ◽  
Vol 26 ◽  
pp. 144-145
Author(s):  
Z. Hruban
Keyword(s):  
Spatial Relationship ◽  
Cell Types ◽  
Deer Mice ◽  
Proximal Tubular Cells ◽  
Slow Loris ◽  
Tubular Cells ◽  
Mitochondrial Inclusions ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

Two types of inclusions in the matrix of mitochondria were observed in our comparative studies on the fine structure of hepatocytes and renal proximal tubular cells of apparently healthy animals. Mitochondrial inclusions occuring in various cell types in healthy and diseased tissues have been recently reviewed by Haust ( Exp. Molec. Pathol. 8: 123, 1968).Multiple small inclusions were seen in the proximal tubular cells of deer mice, Peromyscus boylei (Fig. 1) and P. californicus. These inclusions had an electron lucid center and a narrow dense periphery. Large electron dense inclusions with one or more lucid areas were seen in proximal tubular cells of the slow loris, Nicticebus coucang (Fig. 2). The dense portion of the inclusion was composed of dense laminae about 65 Å thick (Fig. 3). These Inclusions, seen in the deer mice and in the slow loris, are not limited by a membrane and do not show a regular spatial relationship to mitochondrial cristae. The term “lipoid inclusions” is proposed for these structures. Osmiophil intramitochondrial granules are usually absent in mitochondria containing lipoid inclusions. Transitions are found between osmiophil granules and lipoid inclusions.

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