Nephron progenitor cells in development and disease

Dickinson, Kyle; Bernard, Chantal; Iglesias, Diana M.; Goodyer, Paul

doi:10.18103/mra.v10i1.2650

Cited by 2 publications

(1 citation statement)

References 53 publications

(63 reference statements)

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“…The inherent capacity of human kidneys for regeneration and repair after acute injury is an intriguing phenomenon that has been a research focus for many years [1]. Central to this regenerative process is a rare but unique population of kidney progenitor cells that have the capacity to differentiate into multiple renal lineages and are responsible for kidney repair, and can potentially offer therapeutic solutions to renal disease [2,3]. Among these populations of renal progenitor cells, CD133+CD24+ kidney progenitor cells have emerged as a significant player in nephrogenesis and renal regeneration after damage [4,5].…”

Section: Introductionmentioning

confidence: 99%

Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells

Al-Marsoummi,

Mehus,

Shrestha

et al. 2023

IJMS

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Kidney progenitor cells, although rare and dispersed, play a key role in the repair of renal tubules after acute kidney damage. However, understanding these cells has been challenging due to the limited access to primary renal tissues and the absence of immortalized cells to model kidney progenitors. Previously, our laboratory utilized the renal proximal tubular epithelial cell line, RPTEC/TERT1, and the flow cytometry technique to sort and establish a kidney progenitor cell model called Human Renal Tubular Precursor TERT (HRTPT) which expresses CD133 and CD24 and exhibits the characteristics of kidney progenitors, such as self-renewal capacity and multi-potential differentiation. In addition, a separate cell line was established, named Human Renal Epithelial Cell 24 TERT (HREC24T), which lacks CD133 expression and shows no progenitor features. To further characterize HRTPT CD133+CD24+ progenitor cells, we performed proteomic profiling which showed high proteasomal expression in HRTPT kidney progenitor cells. RT-qPCR, Western blot, and flow cytometry analysis showed that HRTPT cells possess higher proteasomal expression and activity compared to HREC24T non-progenitor cells. Importantly, inhibition of the proteasomes with bortezomib reduced the expression of progenitor markers and obliterated the potential for self-renewal and differentiation of HRTPT progenitor cells. In conclusion, proteasomes are critical in preserving progenitor markers expression and self-renewal capacity in HRTPT kidney progenitors.

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Section: Introductionmentioning

confidence: 99%

Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells

Al-Marsoummi,

Mehus,

Shrestha

et al. 2023

IJMS

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WT1 regulates expression of DNA repair gene Neil3 during nephrogenesis

Dickinson

Hammond

Akpa

et al. 2023

American Journal of Physiology-Renal Physiology

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Mammalian nephrons arise from a population of nephron progenitor cells (NPCs) expressing the master transcription factor, WT1, which is crucial for NPC proliferation, migration, and differentiation. In humans, biallelic loss of WT1 precludes nephrogenesis and leads to formation of Wilms tumor precursor lesions. We hypothesize that WT1 normally primes the NPC for nephrogenesis by inducing expression of NPC-specific DNA-repair genes that protect the genome. We analyzed transcript levels for a panel of DNA-repair genes in E17.5 vs adult mouse kidneys and noted seven that were increased >20-fold. We then isolated Cited1(+) NPCs from E17.5 kidneys and found that only one, Neil3, was enriched. RNAscope ISH of E17.5 mouse kidneys showed increased Neil3 expression in the nephrogenic zone vs mature nephron structures. To determine whether Neil3-expression is WT1-dependent, we knocked down Wt1 in Cited1(+) NPCs (60% knockdown efficiency) and noted a 58% reduction in Neil3 transcript levels. We showed that WT1 directly binds to the Neil3 promoter and that activity of a Neil3 promoter-reporter vector was increased two-fold in WT1(+) vs WT1(-) cells. We propose that Neil3 is a WT1-dependent DNA-repair gene, expressed at high levels in Cited1(+) NPCs where it repairs mutational injury to the genome during nephrogenesis. NEIL3 is likely just one of many such lineage-specific repair mechanisms that respond to genomic injury during kidney development.

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Nephron progenitor cells in development and disease

Cited by 2 publications

References 53 publications

Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells

Proteasomes Are Critical for Maintenance of CD133+CD24+ Kidney Progenitor Cells

WT1 regulates expression of DNA repair gene Neil3 during nephrogenesis

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