The Role of Renal Progenitors in Renal Regeneration

Meyer-Schwesinger, Catherine

doi:10.1159/000442180

Cited by 14 publications

(11 citation statements)

References 78 publications

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“…Despite the limited turnover rate of renal cells under physiologic conditions, the adult kidney has some ability to cope with injuries and restore its function. 1 Indeed, human kidneys replace approximately one tubular cell per nephron per day while maintaining normal renal function. 2 However, the mechanisms underlying tubular regeneration are still not fully evaluated.…”

Section: Discussionmentioning

confidence: 99%

Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration

Schießl

Grill

Fremter

et al. 2018

JASN

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Section: Discussionmentioning

confidence: 99%

Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration

Schießl

Grill

Fremter

et al. 2018

JASN

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“…In agreement, previous studies performed by us and other groups strongly suggested that after different modes of kidney injury, regenerating renal cells are not related to BM but originate from resident cells, including vascular, tubular, and interstitial progenitor subpopulations. 22–27 …”

Section: Discussionmentioning

confidence: 99%

Persistent and inducible neogenesis repopulates progenitor renin lineage cells in the kidney

Hickmann

Steglich

Gerlach

et al. 2017

Kidney International

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Renin lineage cells (RLCs) serve as a progenitor cell reservoir during nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool are still poorly understood. Since RLCs were also identified as a progenitor cell population in bone marrow we first considered that these may be their source in the kidney. However, transplantation experiments in adult mice demonstrated that bone marrow-derived cells do not give rise to RLCs in the kidney indicating their non-hematopoietic origin. Therefore we tested whether RLCs develop in the kidney through neogenesis (de novo differentiation) from cells that have never expressed renin before. We used a murine model to track neogenesis of RLCs by flow cytometry, histochemistry, and intravital kidney imaging. During nephrogenesis RLCs first appear at e14, form a distinct population at e16, and expand to reach a steady state level of 8–10% of all kidney cells in adulthood. De novo differentiated RLCs persist as a clearly detectable population through embryogenesis until at least eight months after birth. Pharmacologic stimulation of renin production with enalapril or glomerular injury induced the rate of RLC neogenesis in the adult mouse kidney by 14% or more than three-fold, respectively. Thus, the renal RLC niche is constantly filled by local de novo differentiation. This process could be stimulated consequently representing a new potential target to beneficially influence repair and regeneration after kidney injury.

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“…In fact, there are reports of progressive tubular cell function loss in LS patients [ 57 ]. Although the origin/nature of renewable stem cell-like cells in the post-natal kidney is still controversial [ 64 – 66 ], there is a body of evidence supporting their existence and relevance for maintaining renal functionality [ 66 – 68 ]. Our work suggests the availability of such cell replenishing pool may be compromised in LS patients.…”

Section: Discussionmentioning

confidence: 99%

Kidney-differentiated cells derived from Lowe Syndrome patient’s iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex

et al. 2018

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Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient’s cells from accessible cell types such as skin fibroblasts, and not from the organs affected. This is partially due to the limited accessibility of patient cells from eyes, brain and kidneys. Here we report the preparation of induced pluripotent stem cells (iPSCs) from patient skin fibroblasts and their reprogramming into kidney cells. These reprogrammed kidney cells displayed primary cilia assembly defects similar to those described previously in cell lines. Additionally, the transcription factor and cap mesenchyme marker Six2 was substantially retained in the Golgi complex and the functional nuclear-localized fraction was reduced. These results were confirmed using different batches of differentiated cells from different iPSC colonies and by the use of the human proximal tubule kidney cell line HK2. Indeed, OCRL1 KO led to both ciliogenesis defects and Six2 retention in the Golgi complex. In agreement with Six2’s role in the suppression of ductal kidney lineages, cells from this pedigree were over-represented among patient kidney-reprogrammed cells. We speculate that this diminished efficacy to produce cap mesenchyme cells would cause LS patients to have difficulties in replenishing senescent or damaged cells derived from this lineage, particularly proximal tubule cells, leading to pathological scenarios such as tubular atrophy.

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The Role of Renal Progenitors in Renal Regeneration

Cited by 14 publications

References 78 publications

Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration

Renal Interstitial Platelet-Derived Growth Factor Receptor-β Cells Support Proximal Tubular Regeneration

Persistent and inducible neogenesis repopulates progenitor renin lineage cells in the kidney

Kidney-differentiated cells derived from Lowe Syndrome patient’s iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex

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