Potential renal stem/progenitor cells identified by in vivo lineage tracing DOI
Wenzheng Zhang, Chao Gao,

Akaki Tsilosani

et al.

AJP Renal Physiology, Journal Year: 2022, Volume and Issue: 322(4), P. F379 - F391

Published: Feb. 1, 2022

Mammalian kidneys consist of more than 30 different types cells. A challenging task is to identify and characterize the stem/progenitor subpopulations that establish lineage relationships among these cellular elements during nephrogenesis in embryonic neonate tissue homeostasis and/or injury repair mature kidney. Moreover, potential clinical utility cells holds promise for development new regenerative medicine approaches treatment renal diseases. Stem are defined by unlimited self-renewal capacity pluripotentiality. Progenitor have pluripotentiality but no or limited potential. Cre-LoxP-based vivo genetic tracing a powerful tool their native environment. Hypothetically, this technique enables investigators accurately track progeny single cell group The Cre/LoxP system has been widely used uncover function genes various mammalian tissues through analyses. In review, we summarize recent advances characterization Cre drivers use identifying both developing mouse kidneys.

Language: Английский

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease DOI Creative Commons
Jeffrey W. Pippin, Natalya Kaverina, Yuliang Wang

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(16)

Published: Aug. 14, 2022

With an aging population, kidney health becomes important medical and socioeconomic factor. Kidney mechanisms are not well understood. We previously showed that podocytes isolated from aged mice exhibit increased expression of programmed cell death protein 1 (PD-1) surface receptor its 2 ligands (PD-L1 PD-L2). PDCD1 transcript with age in microdissected human glomeruli, which correlated lower estimated glomerular filtration rate higher segmental glomerulosclerosis vascular arterial intima-to-lumen ratio. In vitro studies demonstrated a critical role for PD-1 signaling survival the induction senescence-associated secretory phenotype. To prove was to podocyte aging, were injected anti–PD-1 antibody. Treatment significantly improved phenotype both liver. glomerulus, it life span podocytes, but parietal epithelial, mesangial, or endothelial cells. Transcriptomic immunohistochemistry antibody treatment podocytes. Administering same young experimental focal (FSGS) lowered proteinuria number. These results suggest contribution toward liver FSGS.

Language: Английский

Citations

54
Podocyte Aging: Why and How Getting Old Matters DOI Open Access
Stuart J. Shankland, Yuliang Wang, Andréy S. Shaw

et al.

Journal of the American Society of Nephrology, Journal Year: 2021, Volume and Issue: 32(11), P. 2697 - 2713

Published: Oct. 29, 2021

The effects of healthy aging on the kidney, and how these intersect with superimposed diseases, are highly relevant in context population's increasing longevity. Age-associated changes to podocytes, which terminally differentiated glomerular epithelial cells, adversely affect kidney health. This review discusses molecular cellular mechanisms underlying podocyte aging, might be augmented by disease aged approaches mitigate progressive damage podocytes. Furthermore, we address biologic pathways such as those associated growth confound humans rodents.

Language: Английский

Citations

42
Single cell landscape of parietal epithelial cells in healthy and diseased states DOI Creative Commons
Wenbin Liu, Guangrui Huang,

Bao‐Li Liu

et al.

Kidney International, Journal Year: 2023, Volume and Issue: 104(1), P. 108 - 123

Published: April 24, 2023

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration crescent formation. Although protein markers have revealed the morphological heterogeneity PECs, molecular characteristics PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis PECs using single-cell RNA sequencing (scRNA-seq) data. Our identified five distinct subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 PEC-B. Among these subpopulations, PEC- A1 PEC-A2 were characterized as progenitors while represented tubular progenitors. Further dynamic signaling network indicated that activation proliferation PEC-A3 played pivotal roles in Analyses suggested upstream signals released by podocytes, immune cells, endothelial mesangial serve pathogenic may be promising intervention targets crescentic glomerulonephritis. Pharmacological blockade two such targets, proteins Mif Csf1r, reduced hyperplasia formation anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates scRNA-seq-based provided valuable insights into pathology therapeutic strategies

Language: Английский

Citations

19
Inhibiting NLRP3 signaling in aging podocytes improves their life- and health-span DOI Creative Commons
Natalya Kaverina, Robert Allen Schweickart, Gek Cher Chan

et al.

Aging, Journal Year: 2023, Volume and Issue: 15(14), P. 6658 - 6689

Published: July 23, 2023

Aging | doi:10.18632/aging.204897. Natalya Kaverina, R. Allen Schweickart, Gek Cher Chan, Joseph C. Maggiore, Diana G. Eng, Yuting Zeng, Sierra McKinzie, Hannah S. Perry, Adilijiang Ali, Christopher O’Connor, Beatriz Maria Veloso Pereira, Ashleigh B. Theberge, Joshua Vaughan, Carol J. Loretz, Anthony Chang, Neil A. Hukriede, Markus Bitzer, Jeffrey W. Pippin, Oliver Wessely, Stuart Shankland

Language: Английский

Citations

14
The Role of Parietal Epithelial Cells in the Pathogenesis of Podocytopathy DOI Creative Commons
Zhihang Li, Xiaoyan Guo, Xiao-ying Quan

et al.

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: March 11, 2022

Podocytopathy is the most common feature of glomerular disorder characterized by podocyte injury- or dysfunction-induced excessive proteinuria, which ultimately develops into glomerulosclerosis and results in persistent loss renal function. Due to lack self-renewal ability podocytes, mild depletion triggers replacement repair processes mostly driven stem cells resident parietal epithelial (PECs). In contrast, when recovery fails, activated PECs contribute establishment lesions. Increasing evidence suggests that PECs, more than just bystanders, have a crucial role various podocytopathies, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic IgA lupus podocytopathy. this review, we attempt dissect diverse pathogenesis podocytopathy based on currently available information.

Language: Английский

Citations

21
PodoCount: A Robust, Fully Automated, Whole-Slide Podocyte Quantification Tool DOI Creative Commons
Briana A. Santo, Darshana Govind, Parnaz Daneshpajouhnejad

et al.

Kidney International Reports, Journal Year: 2022, Volume and Issue: 7(6), P. 1377 - 1392

Published: June 1, 2022

Podocyte depletion is a histomorphologic indicator of glomerular injury and predicts clinical outcomes. estimation methods or podometrics are semiquantitative, technically involved, laborious. Implementation high-throughput in experimental workflows necessitates an automated pipeline. Recognizing that computational image analysis offers robust approach to study cell tissue structure, we developed validated PodoCount (a tool for podocyte quantification immunohistochemically labeled tissues) using diverse data set.Whole-slide images (WSIs) tissues immunostained with nuclear marker periodic acid-Schiff counterstain were acquired. The set consisted murine whole kidney sections (n = 135) from 6 disease models human biopsy specimens patients diabetic nephropathy (DN) 45). Within segmented glomeruli, podocytes extracted was applied compute measures morphometry. Computational performance evaluation statistical testing performed validate podometric associated features. disbursed as open-source, cloud-based tool.PodoCount produced highly accurate when benchmarked against existing methods. profiles identified 0.98 accuracy 0.85 sensitivity 0.99 specificity. Errors count bounded by 1 per glomerulus. Podocyte-specific features found be significant predictors state, proteinuria, outcome.PodoCount high-performance quantitation specimens. Resultant offer correlation metadata outcome. Our will provide end users standardized gigapixel-sized WSIs.

Language: Английский

Citations

21
Central role of podocytes in mediating cellular cross talk in glomerular health and disease DOI

Nehaben A. Gujarati,

Andrew K. Chow,

Sandeep K. Mallipattu

et al.

AJP Renal Physiology, Journal Year: 2024, Volume and Issue: 326(3), P. F313 - F325

Published: Jan. 11, 2024

Podocytes are highly specialized epithelial cells that surround the capillaries of glomeruli in kidney. Together with glomerular endothelial cells, these postmitotic responsible for regulating filtrate from circulating blood their organized network interdigitating foot processes wrap around basement membrane. Although podocyte injury and subsequent loss is hallmark many diseases, recent evidence suggests cell-cell communication between podocytes other nonglomerular critical development progression kidney disease. In this review, we highlight key cellular pathways how they might be a potential target therapy We also postulate serve as central hub under basal conditions response to stress, which may have implications diseases.

Language: Английский

Citations

4
WT1+ glomerular parietal epithelial progenitors promote renal proximal tubule regeneration after severe acute kidney injury DOI Creative Commons

Xizhen Hong,

Hao Nie, Juan Deng

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(4), P. 1311 - 1324

Published: Jan. 1, 2023

Rationale: Mammalian renal proximal tubules can partially regenerate after acute kidney injury (AKI). However, cells participating in the tubule regeneration remain to be elucidated. Wilms' tumor 1 (WT1) expresses a subtype of glomeruli parietal epithelial (PECs) adult kidneys, it remains unclear whether these WT1+ PECs play role regeneration/repair AKI. Methods: Ischemia-reperfusion (IRI) mouse model was used investigate expression pattern WT1 severe Conditional deletion gene mice were generated using Pax8CreERT2 and WT1fl/fl examine function WT1. Then, genetic cell lineage tracing single-cell RNA sequencing performed illustrate that develop into tubular (PTECs). Furthermore, vitro clonogenicity, direct differentiation analysis vivo transplantation reveal stem cell-like properties PECs. Results: The protein PTECs increased aggravated via transient scattered stage, possess specific properties. Conclusions: We discovered group promote AKI, is essential for injury.

Language: Английский

Citations

10
The number and size of glomeruli and podocytes in the aging human kidney DOI Creative Commons
Kotaro Haruhara, Go Kanzaki, Takaya Sasaki

et al.

Kidney International Reports, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
(Zebra)fishing for nephrogenesis genes DOI
Brooke E. Chambers, Nicole E. Weaver, Caroline M. Lara

et al.

Tissue Barriers, Journal Year: 2023, Volume and Issue: 12(2)

Published: May 31, 2023

Kidney disease is a devastating condition affecting millions of people worldwide, where over 100,000 patients in the United States alone remain waiting for lifesaving organ transplant. Concomitant with surge personalized medicine, single-gene mutations, and polygenic risk alleles have been brought to forefront as core causes spectrum renal disorders. With increasing prevalence kidney disease, it imperative make substantial strides field genetics. Nephrons, functional units kidney, are epithelial tubules that act gatekeepers body homeostasis by absorbing secreting ions, water, small molecules filter blood. Each nephron contains series proximal distal segments explicit metabolic functions. The embryonic zebrafish provides an ideal platform systematically dissect genetic cues governing development. Here, we review use discover nephrogenesis genes.

Language: Английский

Citations

9