Fate of iPSCs Derived from Azoospermic and Fertile Men following Xenotransplantation to Murine Seminiferous Tubules

Ramathal, Cyril; Durruthy-Durruthy, Jens; Sukhwani, Meena; Arakaki, Joy; Turek, Paul J.; Orwig, Kyle E.; Pera, Renee A. Reijo

doi:10.1016/j.celrep.2014.03.067

Cited by 91 publications

(82 citation statements)

References 66 publications

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“…Human and monkey SSCs do not regenerate complete spermatogenesis when transplanted into mouse testes. However, they do migrate to the seminiferous tubule basement membrane and produce chains or networks of spermatogonia that persist for many months after transplantation (Hermann et al, 2009; Valli et al, 2014; Izadyar et al, 2011; Zohni et al, 2012; Nagano et al, 2001; Nagano et al, 2002; Hermann et al, 2007; Wu et al, 2009; Sadri-Ardekani et al, 2009; Sadri-Ardekani et al, 2011; Dovey et al, 2013; Clark et al, 2017; Durruthy Durruthy et al, 2014; Ramathal et al, 2014). It is not currently possible to recapitulate complete spermatogenesis from monkey or human cells using the xenotransplantation assays.…”

Section: Ssc Transplantation Bioassay In Higher Primatesmentioning

confidence: 99%

Spermatogonial stem cells and spermatogenesis in mice, monkeys and men

2018

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Continuous spermatogenesis in post-pubertal mammals is dependent on spermatogonial stem cells (SSCs), which balance self-renewing divisions that maintain stem cell pool with differentiating divisions that sustain continuous sperm production. Rodent stem and progenitor spermatogonia are described by their clonal arrangement in the seminiferous epithelium (e.g., Asingle, Apaired or Aaligned spermatogonia), molecular markers (e.g., ID4, GFRA1, PLZF, SALL4 and others) and most importantly by their biological potential to produce and maintain spermatogenesis when transplanted into recipient testes. In contrast, stem cells in the testes of higher primates (nonhuman and human) are defined by description of their nuclear morphology and staining with hematoxylin as Adark and Apale spermatogonia. There is limited information about how dark and pale descriptions of nuclear morphology in higher primates correspond with clone size, molecular markers or transplant potential. Do the apparent differences in stem cells and spermatogenic lineage development between rodents and primates represent true biological differences or simply differences in the volume of research and the vocabulary that has developed over the past half century? This review will provide an overview of stem, progenitor and differentiating spermatogonia that support spermatogenesis; identifying parallels between rodents and primates where they exist as well as features unique to higher primates.

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Section: Ssc Transplantation Bioassay In Higher Primatesmentioning

confidence: 99%

Spermatogonial stem cells and spermatogenesis in mice, monkeys and men

2018

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“…Induced pluripotent stem cells (iPSCs) offer a source of patient-specific stem cells that can be used to study germ cell development in vitro and in vivo 151617181920. Studies using mouse embryonic stem cells (mESCs) have revealed key transcription factors for germ cell specification21.…”

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confidence: 99%

Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies

Dominguez

Chiang

Sukhwani

et al. 2014

Sci Rep

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Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood.

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“…Significantly, the OSKMV-based iPSCs did not form tumors, whereas the OSKM-based iPSCs that remained outside the seminiferous tubule did. The same group also found that hESCs and azoospermia factor (AZF)-deleted hiPSCs inside murine seminiferous tubules could receive critical molecular cues directing germline differentiation; however, outside seminiferous tubules, AZF-deleted iPSCs maintained their undifferentiated state and formed tumors [89]. Thus, these studies suggest that niche cells, potentially Sertoli cells, are critical to suppress somatic cell differentiation and favor the germline fate in hiPSCs.…”

Section: Germ Cell Generation From Niche Repro-grammingmentioning

confidence: 91%

Emerging Methods to Generate Artificial Germ Cells from Stem Cells1

Zeng

Huang

Guo

et al. 2015

Biology of Reproduction

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Germ cells are responsible for the transmission of genetic and epigenetic information across generations. At present, the number of infertile couples is increasing worldwide; these infertility problems can be traced to environmental pollutions, infectious diseases, cancer, psychological or work-related stress, and other factors, such as lifestyle and genetics. Notably, lack of germ cells and germ cell loss present real obstacles in infertility treatment. Recent research aimed at producing gametes through artificial germ cell generation from stem cells may offer great hope for affected couples to treat infertility in the future. Therefore, this rapidly emerging area of artificial germ cell generation from nongermline cells has gained considerable attention from basic and clinical research in the fields of stem cell biology, developmental biology, and reproductive biology. Here, we review the state of the art in artificial germ cell generation.

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Fate of iPSCs Derived from Azoospermic and Fertile Men following Xenotransplantation to Murine Seminiferous Tubules

Cited by 91 publications

References 66 publications

Spermatogonial stem cells and spermatogenesis in mice, monkeys and men

Spermatogonial stem cells and spermatogenesis in mice, monkeys and men

Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies

Emerging Methods to Generate Artificial Germ Cells from Stem Cells1

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