Role of HRTPT in kidney proximal epithelial cell regeneration: Integrative differential expression and pathway analyses using microarray and scRNA‐seq

Shrestha, Swojani; Singhal, Sonalika; Kalonick, Matthew; Guyer, Rachel; Volkert, Alexis; Somji, Seema; Garrett, Scott H.; Sens, Donald A.; Singhal, Sandeep K.

doi:10.1111/jcmm.16976

Cited by 4 publications

(6 citation statements)

References 49 publications

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“…The previous study used HPT cells that showed a marked reduction in 21 lysosomal-and mTOR-related genes, which were used to compare the basal expression of these genes in the HRTPT and HREC24T cells. The HRTPT and HREC24T cells were compared using global gene expression to determine the differentially expressed genes between the two cell lines [11]. This comparison showed that only a few of the 35 lysosomal genes and 15 mTOR genes identified as being altered by elevated glucose concentrations present in either the HRPT or HREC24T cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…The previous study on the HRTPT and HREC24T cells demonstrated only 873 differentially expressed genes between the HRTPT and HREC24T cell lines, narrowing the analysis of the number of genes potentially altered by nephrotoxic agents or conditions. Renal progenitor cells are difficult to study in the intact kidney due to their sparse population and scattered locations [11]. Thus, the present cell lines may help identify factors and mechanisms involved in renal repair in the intact kidney.…”

Section: Discussionmentioning

confidence: 99%

“…There is also an increased risk of RCC in patients with diabetes, providing a potential role of elevated glucose in RCC development [19]. Global gene expression of the HRTPT and HREC24T cells also identified HNF as an upstream regulatory pathway for the HREC24T cells [11]. These observations motivated an examination of the proximal tubule HNF gene in the HRTPT and HREC24T cells exposed to elevated glucose concentrations.…”

Section: Expression Of Hnf Genes In the Hrtpt And Hrec24t Cells Expos...mentioning

confidence: 98%

“…In contrast, the HREC24T cells demonstrated none of these features. Global gene expression analysis has been performed to determine the differential expression of genes between the two cell lines [11].…”

Section: Introductionmentioning

confidence: 99%

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Primary and Immortalized Cultures of Human Proximal Tubule Cells Possess Both Progenitor and Non-Progenitor Cells That Can Impact Experimental Results

Shrestha

Haque

Ighofose

et al. 2023

JPM

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Studies have reported the presence of renal proximal tubule specific progenitor cells which co-express PROM1 and CD24 markers on the cell surface. The RPTEC/TERT cell line is a telomerase-immortalized proximal tubule cell line that expresses two populations of cells, one co-expressing PROM1 and CD24 and another expressing only CD24, identical to primary cultures of human proximal tubule cells (HPT). The RPTEC/TERT cell line was used by the authors to generate two new cell lines, HRTPT co-expressing PROM1 and CD24 and HREC24T expressing only CD24. The HRTPT cell line has been shown to express properties expected of renal progenitor cells while HREC24T expresses none of these properties. The HPT cells were used in a previous study to determine the effects of elevated glucose concentrations on global gene expression. This study showed the alteration of expression of lysosomal and mTOR associated genes. In the present study, this gene set was used to determine if pure populations of cells expressing both PROM1 and CD24 had different patterns of expression than those expressing only CD24 when exposed to elevated glucose concentrations. In addition, experiments were performed to determine whether cross-talk might occur between the two cell lines based on their expression of PROM1 and CD24. It was shown that the expression of the mTOR and lysosomal genes was altered in expression between the HRTPT and HREC24T cell lines based on their PROM1 and CD24 expression. Using metallothionein (MT) expression as a marker demonstrated that both cell lines produced condition media that could alter the expression of the MT genes. It was also determined that PROM1 and CD24 co-expression was limited in renal cell carcinoma (RCC) cell lines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Expression Of Hnf Genes In the Hrtpt And Hrec24t Cells Expos...mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Primary and Immortalized Cultures of Human Proximal Tubule Cells Possess Both Progenitor and Non-Progenitor Cells That Can Impact Experimental Results

Shrestha

Haque

Ighofose

et al. 2023

JPM

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“…Subsequently, our laboratory identified an immortalized human renal proximal tubule epithelial cell line, RPTEC/TERT1, that also displays the two cell populations, one that cell sorting was used to isolate two new immortalized cell lines, one HRTPT that co-expresses PROM1 and CD24, and another, HRECT24T that expresses CD24 and no PROM1 [ 11 ]. The HRTPT cells expressed the features defined for RPCs while the HRECT24T cells displayed no features of RPCs [ 11 , 12 , 13 ]. The HRTPT cells provide a human cell culture model to determine if PROM1/CD24 co-expressing RPCs are susceptible to nephrotoxic agents.…”

Section: Introductionmentioning

confidence: 99%

Arsenite Exposure to Human RPCs (HRTPT) Produces a Reversible Epithelial Mesenchymal Transition (EMT): In-Vitro and In-Silico Study

Singhal

Garrett

Somji

et al. 2023

IJMS

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The human kidney is known to possess renal progenitor cells (RPCs) that can assist in the repair of acute tubular injury. The RPCs are sparsely located as single cells throughout the kidney. We recently generated an immortalized human renal progenitor cell line (HRTPT) that co-expresses PROM1/CD24 and expresses features expected on RPCs. This included the ability to form nephrospheres, differentiate on the surface of Matrigel, and undergo adipogenic, neurogenic, and osteogenic differentiation. These cells were used in the present study to determine how the cells would respond when exposed to nephrotoxin. Inorganic arsenite (iAs) was chosen as the nephrotoxin since the kidney is susceptible to this toxin and there is evidence of its involvement in renal disease. Gene expression profiles when the cells were exposed to iAs for 3, 8, and 10 passages (subcultured at 1:3 ratio) identified a shift from the control unexposed cells. The cells exposed to iAs for eight passages were then referred with growth media containing no iAs and within two passages the cells returned to an epithelial morphology with strong agreement in differential gene expression between control and cells recovered from iAs exposure. Results show within three serial passages of the cells exposed to iAs there was a shift in morphology from an epithelial to a mesenchymal phenotype. EMT was suggested based on an increase in known mesenchymal markers. We found RPCs can undergo EMT when exposed to a nephrotoxin and undergo MET when the agent is removed from the growth media.

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