Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

Bondue, Tjessa; Arcolino, Fanny Oliveira; Veys, Koenraad; Adebayo, Oyindamola C; Levtchenko, Elena; Heuvel, Lambertus P. van den; Elmonem, Mohamed A.

doi:10.3390/cells10061413

Cited by 11 publications

(21 citation statements)

References 212 publications

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“…1e). This observation agrees with clinically known interindividual differences in cell numbers found in urine 34 , while hair follicle output appeared to be due to individual differences in hair texture. All samples were prepared for sequencing using a low-cost in-house library preparation we developed specifically for low-input bulk RNA applications, which uses template-switching oligo (TSO) and tagmentation chemistry and reduces cost by 83% and 68% per reaction compared to the Illumina TruSeq Stranded mRNA Library Prep and SMART-seq V4 kits, respectively (Supp.…”

Section: Noninvasive Tissues Are Amenable To Low-input Library Prepar...supporting

confidence: 90%

“…Though we found urine cell pellets to yield high quality RNA, the pellet itself may be minimal and difficult to visualize for some donors. This is especially true for healthy donors, who tend to shed fewer cells into their urine 34 , and could introduce bias into future study designs if special care is not taken when using this tissue. Similarly, we found urine cell pellet RNA quantity to be variable and donor dependent.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of noninvasive biospecimens for transcriptome studies

Martorella

Kasela

Garcia-Flores

et al. 2022

Preprint

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Transcriptomic studies lend insight into the biology of genetic regulation and bear promise in furthering the goals of precision medicine. However, the cost of RNA-sequencing and types of tissues currently assayed pose major limitations to study expansion and disease-relevant discovery. Here, we develop methods for sampling noninvasive biospecimens for transcriptome studies, investigate their technical and biological characteristics, and assess the feasibility of using noninvasive samples in transcriptomic and clinical applications. Of the four tissues we studied (buccal swabs, hair follicles, saliva, and urine cell pellets), we found hair follicles and urine cell pellets to be most promising due to the consistency of sample quality, underlying biology, and capture of disease-relevant signals. We anticipate future use of noninvasive sampling will facilitate discovery by increasing sample sizes in more diverse populations and in tissues with greater cell type diversity and biological relatedness to disease mechanisms. Moreover, the nature of noninvasive samples enables complex study designs with greater ability to capture context-dependent mechanisms of genetic regulation.

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Section: Noninvasive Tissues Are Amenable To Low-input Library Prepar...supporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Evaluation of noninvasive biospecimens for transcriptome studies

Martorella

Kasela

Garcia-Flores

et al. 2022

Preprint

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“…The strong association between APOL1 gene expression with several non-diabetic chronic kidney diseases and its mechanisms have been extensively investigated using animal or cell models created by gene editing [22,23,27]. Our group has an established methodology to generate stable kidney epithelial lines from cells exfoliated into urine of healthy subjects and patients [30,[40][41][42][43]. Using the same approach, we successfully generated APOL1 G2/G2 podocyte cell model from urine of a human donor carrying APOL1 HRG (G2/G2).…”

Section: Discussionmentioning

confidence: 99%

Novel Human Podocyte Cell Model Carrying G2/G2 APOL1 High-Risk Genotype

Ekulu

Adebayo

Decuypere

et al. 2021

Cells

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Apolipoprotein L1 (APOL1) high-risk genotypes (HRG), G1 and G2, increase the risk of various non-diabetic kidney diseases in the African population. To date, the precise mechanisms by which APOL1 risk variants induce injury on podocytes and other kidney cells remain unclear. Trying to unravel these mechanisms, most studies have used animal or cell models created by gene editing. We developed and characterised conditionally immortalised human podocyte cell lines derived from urine of a donor carrying APOL1 HRG G2/G2. Following induction of APOL1 expression by polyinosinic-polycytidylic acid (poly(I:C)), we assessed functional features of APOL1-induced podocyte dysfunction. As control, APOL1 wild type (G0/G0) podocyte cell line previously generated from a Caucasian donor was used. Upon exposure to poly(I:C), G2/G2 and G0/G0 podocytes upregulated APOL1 expression resulting in podocytes detachment, decreased cells viability and increased apoptosis rate in a genotype-independent manner. Nevertheless, G2/G2 podocyte cell lines exhibited altered features, including upregulation of CD2AP, alteration of cytoskeleton, reduction of autophagic flux and increased permeability in an in vitro model under continuous perfusion. The human APOL1 G2/G2 podocyte cell model is a useful tool for unravelling the mechanisms of APOL1-induced podocyte injury and the cellular functions of APOL1.

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“…Interestingly, the reviewed articles focus on a specific function of the kidney, and, thus, attempt to replicate a specific region of the nephron, rather than the whole unit. Several in vitro cell models that depict different genetic kidney diseases are available and have been extensively reviewed by Bondue et al [10], however not all have been translated to a KOC platform. Indeed, the in vitro modeling of genetic kidney diseases using KOC is in its infancy, and we believe that the current attempts advocate for an adoption of this approach by the research community at large.…”

Section: Kidney Genetic Diseases-on-chipmentioning

confidence: 99%

Organs-on-chip technology: a tool to tackle genetic kidney diseases

et al. 2022

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Chronic kidney disease (CKD) is a major healthcare burden that takes a toll on the quality of life of many patients. Emerging evidence indicates that a substantial proportion of these patients carry a genetic defect that contributes to their disease. Any effort to reduce the percentage of patients with a diagnosis of nephropathy heading towards kidney replacement therapies should therefore be encouraged. Besides early genetic screenings and registries, in vitro systems that mimic the complexity and pathophysiological aspects of the disease could advance the screening for targeted and personalized therapies. In this regard, the use of patient-derived cell lines, as well as the generation of disease-specific cell lines via gene editing and stem cell technologies, have significantly improved our understanding of the molecular mechanisms underlying inherited kidney diseases. Furthermore, organs-on-chip technology holds great potential as it can emulate tissue and organ functions that are not found in other, more simple, in vitro models. The personalized nature of the chips, together with physiologically relevant read-outs, provide new opportunities for patient-specific assessment, as well as personalized strategies for treatment. In this review, we summarize the major kidney-on-chip (KOC) configurations and present the most recent studies on the in vitro representation of genetic kidney diseases using KOC-driven strategies.

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Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

Cited by 11 publications

References 212 publications

Evaluation of noninvasive biospecimens for transcriptome studies

Evaluation of noninvasive biospecimens for transcriptome studies

Novel Human Podocyte Cell Model Carrying G2/G2 APOL1 High-Risk Genotype

Organs-on-chip technology: a tool to tackle genetic kidney diseases

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