Generation of Induced Pluripotent Stem Cells from Human Renal Proximal Tubular Cells with Only Two Transcription Factors, Oct4 and Sox2

Montserrat, Núria; Ramírez-Bajo, María José; Xia, Yun; Sancho‐Martinez, Ignacio; Moya-Rull, Daniel; Miquel-Serra, Laia; Yang, Shenglin; Nivet, Emmanuel; Cortina, Carme; González, Federico; Belmonte, Juan Carlos Izpisúa; Campistol, Josep M.

doi:10.1074/jbc.m112.350413

Cited by 57 publications

(49 citation statements)

References 29 publications

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“…We have cultured urine cells from patients with cryptorchidism and hypospadias, and these cells mainly expressed urothelial surface markers [10]. Genetically normal urine cells and kidney mesangial cells have been successfully reprogrammed during the preparation of this manuscript [29][30][31]. All these results, together with our urine-derived cryptorchid-specific iPS cell lines with genetic variations, demonstrate that urine cells are one of the most acceptable noninvasive sources of iPS cells, especially for research on pediatric diseases.…”

Section: Discussionmentioning

confidence: 88%

Generation and Characterization of Human Cryptorchid-Specific Induced Pluripotent Stem Cells from Urine

Zhou

Wang

Zhang

et al. 2013

Stem Cells and Development

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Cryptorchidism is a common congenital birth defect in human beings with the possible complication of infertility. An in vitro model of cryptorchidism might be valuable due to the inaccessibility of human embryos for research purposes. In this study, we reprogrammed urine cells containing genetic variations in insulin-like factor 3, zinc finger (ZNF) 214, and ZNF215 from a cryptorchid patient by introducing human OCT4, SOX2, C-MYC, and KLF4 with lentivirus. The cells were then replated on irradiated mouse embryonic fibroblasts and cultured with the human embryonic stem (ES) cell medium. The compact colonies with well-defined borders were manually picked, and 2 induced pluripotent cell lines were fully characterized. Our results demonstrated that these 2 cell lines were similar to human ES cells in morphological appearance, marker expression, and epigenetic status of the pluripotent cell-specific gene, OCT4. These cells could be differentiated into cells of all 3 germ layers in teratomas and in vitro, including into the VASA-positive germ cell lineage. Both parental urine cells and the reprogrammed cells possessed the normal karyotype and the same short tandem repeat loci, indicating that these 2 cell population share the same genetic identity. This establishment and characterization of human urinederived cryptorchid-specific induced pluripotent stem cells could present a good human genetic system for future studies investigating the molecular mechanism of cryptorchidism.

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Section: Discussionmentioning

confidence: 88%

Generation and Characterization of Human Cryptorchid-Specific Induced Pluripotent Stem Cells from Urine

Zhou

Wang

Zhang

et al. 2013

Stem Cells and Development

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“…This indicates that iPSC-like tumor cells generated in this study proceeded further in the reprogramming process than the F-class cells (Figure 2D). Similarly to early reports, we found that endogenous expression of reprogramming genes can compensate for ectopic expression (Utikal et al., 2009, Montserrat et al., 2012). This allowed us to reprogram the melanoma cells with OCT4, SOX2, and KLF4 only, without using the oncoprotein MYC.…”

Section: Discussionmentioning

confidence: 99%

Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response

et al. 2017

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SummaryA point mutation in the BRAF gene, leading to a constitutively active form of the protein, is present in 45%–60% of patients and acts as a key driver in melanoma. Shortly after therapy induction, resistance to MAPK pathway-specific inhibitors develops, indicating that pathway inhibition is circumvented by epigenetic mechanisms. Here, we mimicked epigenetic modifications in melanoma cells by reprogramming them into metastable induced pluripotent cancer cells (iPCCs) with the ability to terminally differentiate into non-tumorigenic lineages. iPCCs and their differentiated progeny were characterized by an increased resistance against targeted therapies, although the cells harbor the same oncogenic mutations and signaling activity as the parental melanoma cells. Furthermore, induction of a pluripotent state allowed the melanoma-derived cells to acquire a non-tumorigenic cell fate, further suggesting that tumorigenicity is influenced by the cell state.

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“…79,80 It therefore is important that phenotypes be shown reproducibly in multiple patients, and if possible that rescue experiments be performed to show their specificity. 21 Experiments comparing hiPSCs reprogrammed from urine cells, kidney epithelial cells, or mesangial cells 68,81,82 also should take into account the possibility of injury or secondary mutations in the genitourinary systems of patients with disease, which could affect iPSC function. Recently developed genome editing tools, including transcription activator-like effector nucleases and the Cas9/clustered regularly interspersed short palindromic repeats system, can be applied to hPSCs to introduce or correct genetic mutations for analysis of cellular phenotypes on an isogenic genetic background, and may provide a useful complement to hiPSCs with naturally occurring genetic mutations.…”

Section: Patient-derived Hpsc Methodologies For the Study Of Kidney Dmentioning

confidence: 99%

Directed Differentiation of Pluripotent Stem Cells to Kidney Cells

Lam

Freedman

Bonventre

2014

Seminars in Nephrology

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Summary Regenerative medicine affords a promising therapeutic strategy for the treatment of patients with chronic kidney disease. Nephron progenitor cell populations exist only during embryonic kidney development. Understanding the mechanisms by which these populations arise and differentiate is integral to the challenge of generating new nephrons for therapeutic purposes. Pluripotent stem cells (PSCs), comprising embryonic stem cells, and induced pluripotent stem cells (iPSCs) derived from adults, have the potential to generate functional kidney cells and tissue. Studies in mouse and human PSCs have identified specific approaches to the addition of growth factors, including Wnt and fibroblast growth factor, that can induce PSC differentiation into cells with phenotypic characteristics of nephron progenitor populations with the capacity to form kidney-like structures. Although significant progress has been made, further studies are necessary to confirm the production of functional kidney cells and to promote their three-dimensional organization into bona fide kidney tissue. Human PSCs have been generated from patients with kidney diseases, including polycystic kidney disease, Alport syndrome, and Wilms tumor, and may be used to better understand phenotypic consequences of naturally occurring genetic mutations and to conduct “clinical trials in a dish”. The capability to generate human kidney cells from PSCs has significant translational applications, including the bioengineering of functional kidney tissue, use in drug development to test compounds for efficacy and toxicity, and in vitro disease modeling.

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Generation of Induced Pluripotent Stem Cells from Human Renal Proximal Tubular Cells with Only Two Transcription Factors, Oct4 and Sox2

Cited by 57 publications

References 29 publications

Generation and Characterization of Human Cryptorchid-Specific Induced Pluripotent Stem Cells from Urine

Generation and Characterization of Human Cryptorchid-Specific Induced Pluripotent Stem Cells from Urine

Melanoma-Derived iPCCs Show Differential Tumorigenicity and Therapy Response

Directed Differentiation of Pluripotent Stem Cells to Kidney Cells

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