Sall1 balances self-renewal and differentiation of renal progenitor cells

AbstractBackgroundHuman urine is now recognised as a non-invasive source of stem cells with regeneration potential. These cells are mesenchymal stem cells but their detailed molecular and cellular identities are poorly defined. Furthermore, unlike the mouse, the gene regulatory network driving self-renewal and differentiation into functional renal cells in vitro remain unresolved.MethodsWe isolated urine stem cells from 10 individuals from both genders and distinct ages, characterized them as renal progenitor cells and explored the gene regulatory network sustaining self-renewal.ResultsThese cells express pluripotency-associated proteins-TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133. Expression of pluripotency-associated proteins enabled rapid reprogramming into iPSCs using episomal-based plasmids without pathway perturbations. Transcriptome analysis revealed expression of a plethora of nephrogenesis-related genes such as SIX2, OSR1, CITED1, NPHS2, NPHS1, PAX2, SALL1, AQP2, EYA1, SLC12A1 and UMOD. As expected, the cells transport Albumin by endocytosis. Based on this, we refer to these cells as urine derived renal progenitor cells-UdRPCs. Associated GO-term analysis of UdRPCs and UdRPC-iPSCs underlined their renal identity and functionality. Upon differentiation by WNT activation using the GSK3β-inhibitor (CHIR99021), transcriptome and KEGG pathway analysis revealed upregulation of WNT-associated genes-AXIN2, JUN and NKD1. Protein interaction network identified JUN- a downstream target of the WNT pathway in association with STAT3, ATF2 and MAPK1 as a putative regulator of self-renewal and differentiation in UdRPCs. Furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway.ConclusionThis in vitro model and the data presented should lay the foundation for studying nephrogenesis in man.Significance StatementHuman urine is a non-invasive source of stem cells with regeneration potential. Here, we investigated the cellular and molecular identities, and the gene regulation driving self-renewal and differentiation of these cells in vitro. These cells express pluripotency-associated markers enabling easy reprogramming. Based on the expression of renal associated genes, proteins and functionality, we refer to these cells as urine derived renal progenitor cells-UdRPCs. CHIR99021-induced differentiation of UdRPCs activated WNT-related genes-AXIN2, JUN and NKD1. Protein interaction network identified JUN as a putative regulator of differentiation whereas self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3. Our data will enhance understanding of the molecular identities of UdRPCs, and enable the generation of renal disease models in vitro and eventually kidney-associated regenerative therapies.

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Kidney bioengineering by using decellularized kidney scaffold and renal progenitor cells

Tissue and Cell ◽

10.1016/j.tice.2021.101699 ◽

2021 ◽

pp. 101699

Author(s):

Chih-Yang Hsu ◽

Pei-Ling Chi ◽

Hsin-Yu Chen ◽

Shih-Hsiang Ou ◽

Kang-Ju Chou ◽

...

Keyword(s):

Progenitor Cells ◽

Renal Progenitor Cells ◽

Renal Progenitor

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Erratum for the Research Article: “Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells” by A. J. Peired, G. Antonelli, M. L. Angelotti, M. Allinovi, F. Guzzi, A. Sisti, R. Semeraro, C. Conte, B. Mazzinghi, S. Nardi, M. E. Melica, L. De Chiara, E. Lazzeri, L. Lasagni, T. Lottini, S. Landini, S. Giglio, A. Mari, F. Di Maida, A. Antonelli, F. Porpiglia, R. Schiavina, V. Ficarra, D. Facchiano, M. Gacci, S. Serni, M. Carini, G. J. Netto, R. M. Roperto, A. Magi, C. F. Christiansen, M. Rotondi, H. Liapis, H.-J. Anders, A. Minervini, M. R. Raspollini, P. Romagnani

Science Translational Medicine ◽

10.1126/scitranslmed.abd2685 ◽

2020 ◽

Vol 12 (549) ◽

pp. eabd2685

Keyword(s):

Acute Kidney Injury ◽

Progenitor Cells ◽

Renal Cell ◽

Kidney Injury ◽

Cell Adenoma ◽

Renal Progenitor Cells ◽

Research Article ◽

Renal Progenitor

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Role of bone marrow-derived stem cells, renal progenitor cells and stem cell factor in chronic renal allograft nephropathy

Alexandria Journal of Medicine ◽

10.1016/j.ajme.2013.01.002 ◽

2013 ◽

Vol 49 (3) ◽

pp. 235-247

Author(s):

Hayam Abdel Meguid El Aggan ◽

Mona Abdel Kader Salem ◽

Nahla Mohamed Gamal Farahat ◽

Ahmad Fathy El-Koraie ◽

Ghaly Abd Al-Rahim Mohammed Kotb

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Progenitor Cells ◽

Stem Cell Factor ◽

Renal Allograft ◽

Renal Progenitor Cells ◽

Renal Progenitor

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Organogenesis of kidneys following transplantation of renal progenitor cells

Transplant Immunology ◽

10.1016/j.trim.2003.12.002 ◽

2004 ◽

Vol 12 (3-4) ◽

pp. 229-239 ◽

Cited By ~ 20

Author(s):

Marc R Hammerman

Keyword(s):

Progenitor Cells ◽

Renal Progenitor Cells ◽

Renal Progenitor

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miR-1915 and miR-1225-5p Regulate the Expression of CD133, PAX2 and TLR2 in Adult Renal Progenitor Cells

PLoS ONE ◽

10.1371/journal.pone.0068296 ◽

2013 ◽

Vol 8 (7) ◽

pp. e68296 ◽

Cited By ~ 31

Author(s):

Fabio Sallustio ◽

Grazia Serino ◽

Vincenzo Costantino ◽

Claudia Curci ◽

Sharon N. Cox ◽

...

Keyword(s):

Progenitor Cells ◽

Renal Progenitor Cells ◽

Renal Progenitor

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Experimental renal progenitor cells: Repairing and recreating kidneys?

Pediatric Nephrology ◽

10.1007/s00467-013-2667-5 ◽

2013 ◽

Vol 29 (4) ◽

pp. 665-672 ◽

Cited By ~ 7

Author(s):

Paul J. D. Winyard ◽

Karen L. Price

Keyword(s):

Progenitor Cells ◽

Renal Progenitor Cells ◽

Renal Progenitor

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Renal Progenitor Cells Have Higher Genetic Stability and Lower Oxidative Stress than Mesenchymal Stem Cells during In Vitro Expansion

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6470574 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Elís Rosélia Dutra de Freitas Siqueira Silva ◽

Napoleão Martins Argôlo Neto ◽

Dayseanny de Oliveira Bezerra ◽

Sandra Maria Mendes de Moura Dantas ◽

Lucilene dos Santos Silva ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Dna Damage ◽

Mesenchymal Stem Cells ◽

Progenitor Cells ◽

Genetic Stability ◽

Renal Progenitor Cells ◽

In Vitro Expansion ◽

Renal Progenitor

In vitro senescence of multipotent cells has been commonly associated with DNA damage induced by oxidative stress. These changes may vary according to the sources of production and the studied lineages, which raises questions about the effect of growing time on genetic stability. This study is aimed at evaluating the evolution of genetic stability, viability, and oxidative stress of bone marrow mesenchymal stem cells (MSCBMsu) and renal progenitor cells of the renal cortex (RPCsu) of swine (Sus scrofa domesticus) in culture passages. P2, P5, and P9 were used for MSCBMsu and P1, P2, and P3 for RPCsu obtained by thawing. The experimental groups were submitted to MTT, apoptosis and necrosis assays, comet test, and reactive substance measurements of thiobarbituric acid (TBARS), nitrite, reduced glutathione (GSH), and catalase. The MTT test curve showed a mean viability of 1.14±0.62 and 1.12±0.54, respectively, for MSCBMsu and RPCsu. The percentages of MSCBMsu and RPCsu were presented, respectively, for apoptosis, an irregular and descending behavior, and necrosis, ascending and irregular. The DNA damage index showed higher intensity among the MSCBMsu in the P5 and P9 passages (p<0.05). In the TBARS evaluation, there was variation among the lines of RPCsu and MSCBMsu, presenting the last most significant variations (p<0.05). In the nitrite values, we identified only among the lines, in the passages P1 and P2, with the highest averages displayed by the MSCBMsu lineage (p<0.05). The measurement of antioxidant system activity showed high standards, identifying differences only for GSH values, in the RPCsu lineage, in P3 (p<0.05). This study suggests that the maintenance of cell culture in the long term induces lower regulation of oxidative stress, and RPCsu presents higher genetic stability and lower oxidative stress than MSCBMsu during in vitro expansion.

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