Reprogramming of adult human testicular cells by four transcription factors (OCT4, SOX2, KLF4, and C‐MYC)

Kobayashi, Hideyuki; Nakajima, Koichi; Oka, Yusuke; Tai, Toshihiro; Nagao, Kōichi; Ishii, Nobuhisa

doi:10.1007/s12522-011-0077-6

Cited by 4 publications

(4 citation statements)

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“…Here we developed KS-derived iPS cells, which could be useful for mechanistic studies of KS. We previously generated iPS cells derived from adult human testicular tissue using lentiviral vectors expressing OCT4, SOX2, KLF4, and C-MYC [15]. We also succeeded in generating iPS cells derived from the testicular tissue of a KS patient using the same system [6].…”

Section: Discussionmentioning

confidence: 99%

Derivation of integration‐free iPSCs from a Klinefelter syndrome patient

Shimizu

Shiohara

Tai

et al. 2015

Reprod Medicine & Biology

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PurposeKlinefelter syndrome (KS) (47, XXY) is the most common sex chromosome abnormality in humans. KS is characterized by gynecomastia, tall stature, small testes, low testosterone levels, learning disabilities, and behavioral problems. KS is also associated with infertility due to non-obstructive azoospermia (NOA). The mechanism underlying NOA is still poorly understood, and although there is no current treatment, the use of microdissection testicular sperm extraction (micro-TESE) followed by in vitro fertilization can result in successful conception. The generation of induced pluripotent stem (iPS) cells derived from KS patients may be useful for studying the disease mechanism and identifying novel therapies.MethodsCells from a KS patient were transduced with Sendai viral vectors encoding four transcription factors, OCT4, SOX2, KLF4, and C-MYC, and the transduced cells were analyzed for in vitro and in vivo pluripotency.ResultsKS patient-derived iPS cells were successfully generated and shown to produce teratomas in the testes of SCID mice. In vitro differentiation of the iPS cells into cardiomyocyte-like cells was confirmed by the presence of clusters of beating cells.ConclusionsKS patient-derived iPS cells that could differentiate into cardiomyocyte-like cells were established.Electronic supplementary materialThe online version of this article (doi:10.1007/s12522-015-0213-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Derivation of integration‐free iPSCs from a Klinefelter syndrome patient

Shimizu

Shiohara

Tai

et al. 2015

Reprod Medicine & Biology

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“…Human iPSCs have remarkable similarities to human embryonic stem cells (hESCs) in terms of their morphology, culture, proliferation, gene expression, and ability to differentiate into mesoderm, endoderm, and ectoderm both in vitro and in teratoma assays in vivo [53,54]. We induced iPS cells from adult human testicular tissue by introducing OCT4, SOX2, KLF4, and C-MYC, using lentiviral vectors [55]. In addition, we generated ES-like cells from 293FT cells by introducing OCT4, SOX2, NANOG, and LIN28 with lentiviral vectors [56].…”

Section: Induced Pluripotent Stem (Ips) Cellsmentioning

confidence: 99%

Therapeutic advances in the field of male infertility: stem cell research

Kobayashi¹,

Nagao²,

Nakajima³

2013

asms

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A male factor is involved in 50% of infertile relationships. In particular, men with nonobstructive azoospermia cannot have their own biological children. The treatment is microdissection testicular sperm extraction, but the success rate is low, and new approaches for male infertility are needed. Stem cells have the potential to differentiate into different functional cell types, and their discovery has given rise to the field of regenerative medicine. We focus here on the therapeutic potential of stem cells for rejuvenating male fertility. Embryonic stem cells (ESCs) can differentiate directly into male or female gametes, but they are genetically unrelated to the patient. Spermatogonial stem cells (SSCs) undergo self-renewal and differentiation in the adult testis, and maintain normal spermatogenesis. SSCs can acquire pluripotency and differentiate into the three embryonic germ layers. Mammalian somatic cells can be reprogrammed as induced pluripotent stem cells (iPSCs) by introducing a small set of 40 H. Kobayashi, K. Nagao and K. Nakajima transcription factors. Germline differentiation has been achieved in hESCs and iPSCs by the subsequent forced overexpression of DAZ-family genes. One group has directed the differentiation of iPSCs to germ-like cells without the overexpression of development-related genes. Stem-cell research has great potential for clinical applications, including treatments for male infertility.

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“…In our laboratory, we induced iPS cells from adult human testicular tissue by introducing four transcription factors, OCT4, SOX2, KLF4, and C-MYC, using lentiviral vectors [58]. We also generated ES-like cells from 293FT cells by using OCT4, SOX2, NANOG, and LIN28 [59].…”

Section: Induced Pluripotent Stem (Ips) Cellsmentioning

confidence: 99%