A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells

Ding, Zicheng; Sui, Lina; Ren, Rui; Liu, Yanjun; Xu, Xiuling; Fu, Ling; Bai, Ruijun; Yuan, Tingting; Hao, Ying; Zhang, Weiqi; Pan, Huize; Liu, Wensu; Han, Yu; Esteban, Concepción Rodrı́guez; Yu, Xiaobing; Yang, Ze; Li, Jian; Wang, Xiaomin; Belmonte, Juan Carlos Izpisúa; Liu, Guanghui; Yi, Fei; Qu, Jing

doi:10.1007/s13238-014-0117-1

Cited by 13 publications

(14 citation statements)

References 15 publications

(23 reference statements)

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“…Electron microscopy. Electron microscopy was performed at the Center for Biological Imaging of the Chinese Academy of Sciences using a FEI Tecnai T12 G2 transmission electron microscope 44 .…”

Section: Methodsmentioning

confidence: 99%

A single-cell transcriptomic landscape of primate arterial aging

et al. 2020

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Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevityassociated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders.

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Section: Methodsmentioning

confidence: 99%

A single-cell transcriptomic landscape of primate arterial aging

et al. 2020

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“…1B). To generate patient-specific iPSCs (CS-iPSCs), a cocktail of integration-free episomal vectors expressing the reprogramming factors OCT4, SOX2, KLF4, L-MYC, LIN28, and sh-p53 was electroporated into fibroblasts according to a modified reprogramming protocol, as previously described (Hishiya and Watanabe, 2004;Okita et al, 2011;Liu et al, 2014;Ding et al, 2015;Fu et al, 2016;Wang et al, 2017;Ling et al, 2019). The derived iPSCs displayed normal karyotypes, and no residual episomal reprogramming vector element was detected in established CS-iPSCs ( Fig.…”

Section: Generation Of Non-integrative Ipscs From a Cs Patientmentioning

confidence: 99%

Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Wang

Min

et al. 2019

Protein Cell

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Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and

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“…2 A–F), despite the fact that XPC was reported as an Oct4/Sox2 coactivator by forming a protein complex in embryonic stem cells (Cattoglio et al, 2015 ). In addition, an iPSC line reprogrammed from healthy (WT) human fibroblasts was used as a control (Ding et al, 2015 ). All the derived iPSCs exhibited normal karyotype and expressed comparable levels of the pluripotency markers including NANOG, OCT4, and SOX2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

Ren

et al. 2016

Protein Cell

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Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

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A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells

Cited by 13 publications

References 15 publications

A single-cell transcriptomic landscape of primate arterial aging

A single-cell transcriptomic landscape of primate arterial aging

Rescue of premature aging defects in Cockayne syndrome stem cells by CRISPR/Cas9-mediated gene correction

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

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