Targeted single-cell RNA-seq identifies minority cell types of kidney distal nephron that regulate blood pressure and calcium balance

Chen, Lihe; Chou, Chung‐Lin; Knepper, Mark A.

doi:10.1101/2020.07.19.209627

Cited by 3 publications

(7 citation statements)

References 74 publications

(105 reference statements)

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“…Several studies have shown that Cldn3 mRNA is expressed in the mouse S2 and S3 proximal tubules 40–43,47 . Weak or no Cldn3 mRNA expression was found in proximal tubules in other study, however 44,45 .…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 59%

“…Cldn1 mRNA is expressed in mouse proximal tubule, 37,40–43,47 whereas in other studies, weak Cldn1 expression was detected in mouse and rat proximal tubule 44,45,49,50 . No expression of CLDN1 mRNA was detected in the human proximal tubule 54,55 .…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 60%

“…Cldn12 mRNA is expressed in the mouse proximal tubule 37,40–45 . A low level of CLDN12 mRNA expression is also observed in the human proximal straight tubule 54 .…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 90%

“…Claudin10 is expressed in various tubular segments, including the proximal tubule in mouse, 36,37,40–43,46,64 in rat, 49–52,64 and in human, 54–56,64 as shown by analyses at the mRNA and protein levels. No antibody is available to distinguish between CLDN10a and CLDN10b proteins, which differ in transmembrane helix 1 and part of the first extracellular loop; however, mRNA expression studies in mouse kidney showed that Cldn10a mRNA is expressed in the proximal tubule and Cldn10b in the TAL 28,38,65,66 .…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 94%

“…In patients with the latter disease, the plasma Mg concentration has not been reported. Claudin 2 mRNA and protein are expressed in the proximal tubule in mouse 28,36,40–48 and rat 49–52 . Kiuchi‐Saishin et al.…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 99%

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Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia

Houillier

Lievre

Hureaux

et al. 2023

Annals of the New York Academy of Sciences

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Magnesium is the fourth most abundant cation in the body. It plays a critical role in many biological processes, including the process of energy release. Paracellular transport of magnesium is mandatory for magnesium homeostasis. In addition to intestinal absorption that occurs in part across the paracellular pathway, magnesium is reabsorbed by the kidney tubule. The bulk of magnesium is reabsorbed through the paracellular pathway in the proximal tubule and the thick ascending limb of the loop of Henle. The finding that rare genetic diseases due to pathogenic variants in genes encoding specific claudins (CLDNs), proteins located at the tight junction that determine the selectivity and the permeability of the paracellular pathway, led to an awareness of their importance in magnesium homeostasis. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is caused by a loss of function of CLDN16 or CLDN19. Pathogenic CLDN10 variants cause HELIX syndrome, which is associated with a severe renal loss of sodium chloride and hypermagnesemia. The present review summarizes the current knowledge of the mechanisms and factors involved in paracellular magnesium permeability. The review also highlights some of the unresolved questions that need to be addressed. K E Y W O R D Sclaudin, familial hypomagnesemia with hypercalciuria and nephrocalcinosis, HELIX syndrome, paracellular ion transport, tight junction Magnesium (Mg) a is the fourth most abundant cation in vertebrates and the second most abundant intracellular cation. Mg homeostasis is mandatory as Mg 2+ is involved in many biological processes.Mg 2+ plays a critical role in the release of chemical energy: Adenosine triphosphate (ATP) is formed by Mg-dependent oxidative phosphorylaa Mg 2+ , free magnesium; Mg, elemental magnesium, including free magnesium and magnesium stably bound to anions, proteins, or nucleic acids.

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Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 59%

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 60%

“…Cldn12 mRNA is expressed in the mouse proximal tubule 37,40–45 . A low level of CLDN12 mRNA expression is also observed in the human proximal straight tubule 54 .…”

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 90%

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 94%

Section: Paracellular Renal Tubular Transport Of Magnesiummentioning

confidence: 99%

See 3 more Smart Citations

Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia

Houillier

Lievre

Hureaux

et al. 2023

Annals of the New York Academy of Sciences

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A reference tissue atlas for the human kidney

Hansen

Sealfon

Menon

et al. 2020

Preprint

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The Kidney Precision Medicine Project (KPMP) plans to construct a spatially specified tissue atlas of the human kidney at a cellular resolution with near comprehensive molecular details. The atlas will have maps of healthy, acute kidney injury and chronic kidney disease tissues. To construct such maps, we integrate different data sets that profile mRNAs, proteins and metabolites collected by five KPMP Tissue Interrogation Sites. Here, we describe a set of hierarchical analytical methods to process, combine, and harmonize single-cell, single-nucleus and subsegmental laser microdissection (LMD) transcriptomics with LMD and near single-cell proteomics, 3-D nondestructive and immunofluorescence-based Codex imaging and spatial metabolomics datasets. We use nephrectomy, healthy living donor and surveillance transplant biopsy tissues to create a harmonized reference tissue map. Our results demonstrate that different assays produce reliable and coherent identification of cell types and tissue subsegments. They further show that the molecular profiles and pathways are partially overlapping yet complementary for cell type-specific and subsegmental physiological processes. Focusing on the proximal tubules, we find that our integrated systems biologybased analyses identify different subtypes of tubular cells with potential for different levels of lipid oxidation and energy generation. Integration of our omics data with pathways from the literature, enables us to construct predictive computational models to develop a smart kidney atlas. These integrated models can describe physiological capabilities of the tissues based on the underlying cell types and pathways in health and disease.

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HIV viral protein R induces loss of DCT1-type renal tubules

Latt

Yoshida

Shrivastav

et al. 2023

Preprint

Self Cite

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HIV viral protein R (Vpr) contributes to HIV-associated nephropathy, induces cell cycle arrest, and alters expression of mineralocorticoid-responsive genes. To investigate Vpr modulation of aldosterone-mediated regulation of the expression of Na-Cl cotransporter Slc12a3 and sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices of wild-type (WT) and Vpr transgenic (Vpr Tg) mice on low sodium diet and a WT mouse on regular chow. In Vpr Tg mouse, Slc12a3 expression was downregulated in connecting tubules (CNT) and late distal convoluted tubules (DCT2) but not in early DCT (DCT1). Mineralocorticoid receptor (Nr3c2) expression was higher in CNT and DCT2 than in DCT1. DCT1 cell percentage in salt-depleted Vpr Tg was lower (1.8%) compared with salt-depleted or salt-replete WT (3.7% and 3.6%, respectively). Sub-clustering confirmed that Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg (0.95%) compared with salt-depleted or salt-replete WT (2.9% and 3.1%, respectively). Autophagy and protein ubiquitination genes were upregulated in DCT1 subcluster of Vpr Tg mice. In situ hybridization and immunohistochemistry demonstrated fewer Slc12a3+ Pvalb+ DCT1 segments in Vpr Tg mice. Downregulation of Slc12a3 and higher levels of Nr3c2 in the CNT/DCT2 suggested that the aldosterone-mediated upregulation of Slc12a3 with salt depletion was most prominently inhibited by Vpr in the CNT/DCT2. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3+ Pvalb+ DCT1 segments. The downregulation of Slc12a3 occurred in more distal segments rather than in DCT1.

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Targeted single-cell RNA-seq identifies minority cell types of kidney distal nephron that regulate blood pressure and calcium balance

Cited by 3 publications

References 74 publications

Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia

Mechanisms of paracellular transport of magnesium in intestinal and renal epithelia

A reference tissue atlas for the human kidney

HIV viral protein R induces loss of DCT1-type renal tubules

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