Generation of Human Induced Pluripotent Stem Cells from Liver Progenitor Cells by Only Small Molecules†

Moriguchi, Hiroyuki; Raymond, Tamara; Mihara, Makoto; Sato, Chifumi

doi:10.1002/hep.23851

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…iMSC were previously described and iLC2 were newly derived, by retroviral transduction of LC2 with Oct4, Sox2, Klf4 and c-Myc, as described in Section 2 [23,25-27]. Both iLC2 and iMSC demonstrate classical iPSC features, including their morphology in culture, TRA-1-60 staining, and cystic teratoma formation with three germ layer derivatives (Figure S1A–D) [25]. Induced LC2 and iMSC expressed endogenous transcriptional regulators and cell-surface markers characteristic of hESC, including NANOG, OCT4, SSEA-4, and TRA-1-60 (Figure S1A) [25].…”

Section: Resultsmentioning

confidence: 99%

“…Both iLC2 and iMSC demonstrate classical iPSC features, including their morphology in culture, TRA-1-60 staining, and cystic teratoma formation with three germ layer derivatives (Figure S1A–D) [25]. Induced LC2 and iMSC expressed endogenous transcriptional regulators and cell-surface markers characteristic of hESC, including NANOG, OCT4, SSEA-4, and TRA-1-60 (Figure S1A) [25]. Overall, the expression of stem cell markers in iLC2 was indistinguishable from hESC we examined, H1 and H9, maintained under the same conditions [23].…”

Section: Resultsmentioning

confidence: 99%

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Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

Fan

Robert

Jang

et al. 2011

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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To maintain the integrity of the organism, embryonic stem cells (ESC) need to maintain their genomic integrity in response to DNA damage. DNA double strand breaks (DSBs) are one of the most lethal forms of DNA damage and can have disastrous consequences if not repaired correctly, leading to cell death, genomic instability and cancer. How human ESC (hESC) maintain genomic integrity in response to agents that cause DSBs is relatively unclear. Adult somatic cells can be induced to "dedifferentiate" into induced pluripotent stem cells (iPSC) and reprogram into cells of all three germ layers. Whether iPSC have reprogrammed the DNA damage response is a critical question in regenerative medicine. Here, we show that hESC demonstrate high levels of endogenous reactive oxygen species (ROS) which can contribute to DNA damage and may arise from high levels of metabolic activity. To potentially counter genomic instability caused by DNA damage, we find that hESC employ two strategies: First, these cells have enhanced levels of DNA repair proteins, including those involved in repair of DSBs, and they demonstrate elevated nonhomologous end-joining (NHEJ) activity and repair efficacy, one of the main pathways for repairing DSBs. Second, they are hypersensitive to DNA damaging agents, as evidenced by a high level of apoptosis upon irradiation. Importantly, iPSC, unlike the parent cells they are derived from, mimic hESC in their ROS levels, cell cycle profiles, repair protein expression and NHEJ repair efficacy, indicating reprogramming of the DNA repair pathways. Human iPSC however show a partial apoptotic response to irradiation, compared to hESC. We suggest that DNA damage responses may constitute important markers for the efficacy of iPSC reprogramming.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

Fan

Robert

Jang

et al. 2011

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

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Induced pluripotent stem cells for modeling of pediatric neurological disorders

Jang

Quan

Yum

et al. 2014

Biotechnology Journal

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The pathophysiological mechanisms underlying childhood neurological disorders have remained obscure due to a lack of suitable disease models reflecting human pathogenesis. Using induced pluripotent stem cell (iPSC) technology, various neurological disorders can now be extensively modeled. Specifically, iPSC technology has aided the study and treatment of early-onset pediatric neurodegenerative diseases such as Rett syndrome, Down syndrome, Angelman syndrome. Prader-Willi syndrome, Friedreich's ataxia, spinal muscular atrophy (SMA), fragile X syndrome, X-linked adrenoleukodystrophy (ALD), and SCN1A gene-related epilepsies. In this paper, we provide an overview of various gene delivery systems for generating iPSCs, the current state of modeling early-onset neurological disorders and the ultimate application of these in vitro models in cell therapy through the correction of disease-specific mutations.

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Potential therapeutic applications of differentiated induced pluripotent stem cells (iPSCs) in the treatment of neurodegenerative diseases

et al. 2013

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Generation of Human Induced Pluripotent Stem Cells from Liver Progenitor Cells by Only Small Molecules†

Cited by 6 publications

References 30 publications

Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

Human induced pluripotent cells resemble embryonic stem cells demonstrating enhanced levels of DNA repair and efficacy of nonhomologous end-joining

Induced pluripotent stem cells for modeling of pediatric neurological disorders

Potential therapeutic applications of differentiated induced pluripotent stem cells (iPSCs) in the treatment of neurodegenerative diseases

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