Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules

Yang, Shi; Bo, Juan-jie; Hu, Haidong; Guo, Xizhi; Tian, Ruhui; Sun, Chao; Zhu, Yong; Li, P.; Liu, P.; Zou, Shasha; Huang, Yigang; Li, Zida

doi:10.1111/j.1365-2184.2012.00811.x

Cited by 56 publications

(56 citation statements)

References 40 publications

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“…MVH is a specific marker for germ cells from the late migration stage to the postmeiotic stage and it plays an essential role in germ cell specification, proliferation and maintenance [Tanaka et al, 2000;Tilgner et al, 2010;Tian et al, 2011;Yang et al, 2012]. Using immunohistochemical analysis, Western blots and real-time PCR, we observed that MVH was expressed at higher levels in regenerated tubules from VEGF-treated grafts compared to SU5416-treated grafts, suggesting that VEGF/VEGFR 2 signaling plays an important role in testicular regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…MVH (also known as VASA) is a specific germ cell marker expressed in the cytoplasm of germ cells from spermatogonia to spermatids [Tian et al, 2011;Yang et al, 2012]. Immunohistochemistry revealed that MVH was expressed in the regenerated tubules of all groups, suggesting that male germ cells reside in the tubules and undergo proliferation and differentiation ( fig.…”

Section: Mvh Expression Analysis Of Regenerated Seminiferous Testis Bmentioning

confidence: 99%

“…Mvh is considered to be the most liable germ cell marker [Tian et al, 2011;Yang et al, 2012], while Stra8 is a premi- totic germ cell hallmark [Kimble, 2011]. Dazl and Boule belong to the DAZ family and are mainly expressed in germ cells [Kim et al, 2012], and Soggy can be detected in male germ cells from spermatocytes to sperm [Kaneko and DePamphilis, 2000;Kohn et al, 2005].…”

Section: Qpcr Analysis Of Genes In the Regenerated Testicularmentioning

confidence: 99%

“…Ectopic testicular transplantation has been accomplished in various species, including mice, rats, pigs and sheep [Gassei et al, 2006;Dobrinski, 2007;Honaramooz et al, 2007;Kita et al, 2007;Arregui et al, 2008;Gassei et al, 2010;Tian et al, 2011;Yang et al, 2012]. It provides a unique tool with which to investigate the basic mechanisms of testis development and sperm production.…”

Section: Introductionmentioning

confidence: 99%

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VEGF/VEGFR2 Signaling Regulates Germ Cell Proliferation in vitro and Promotes Mouse Testicular Regeneration in vivo

Tian

Yang

Zhu

et al. 2016

Cells Tissues Organs

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Vascular endothelial growth factor (VEGF) plays fundamental roles in testicular development; however, its function on testicular regeneration remains unknown. The objective of this study was to explore the roles VEGF/VEGFR₂ signaling plays in mouse germ cells and in mouse testicular regeneration. VEGF and the VEGFR₂ antagonist SU5416 were added to culture medium to evaluate their effects on spermatogonial stem cell line (C18-4 cells) proliferation. Testicular cells obtained from newborn male ICR mice were grafted into the dorsal region of male BALB/c nude mice. VEGF and SU5416 were injected into the graft sites to assess the effects of the VEGF and VEGFR₂ signaling pathways on testicular reconstitution. The grafts were analyzed after 8 weeks. We found that VEGF promoted C18-4 proliferation in vitro, indicating its role in germ cell survival. HE staining revealed that seminiferous tubules were reconstituted and male germ cells from spermatogonia to spermatids could be observed in testis-like tissues 8 weeks after grafting. A few advantaged male germ cells, including spermatocytes and spermatids, were found in SU5416-treated grafts. Moreover, VEGF enhanced the expression of genes specific for male germ cells and vascularization in 8-week grafts, whereas SU5416 decreased the expression of these genes. SU5416-treated grafts had a lower expression of MVH and CD31, indicating that blockade of VEGF/VEGFR₂ signaling reduces the efficiency of seminiferous tubule reconstitution. Collectively, these data suggest that VEGF/VEGFR₂ signaling regulates germ cell proliferation and promotes testicular regeneration via direct action on germ cells and the enhancement of vascularization.

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Section: Discussionmentioning

confidence: 99%

Section: Mvh Expression Analysis Of Regenerated Seminiferous Testis Bmentioning

confidence: 99%

Section: Qpcr Analysis Of Genes In the Regenerated Testicularmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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VEGF/VEGFR2 Signaling Regulates Germ Cell Proliferation in vitro and Promotes Mouse Testicular Regeneration in vivo

Tian

Yang

Zhu

et al. 2016

Cells Tissues Organs

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“…Generally, there are two methods to produce male gametes from the pluripotent stem cells in vitro [20]: the monolayer differentiation and the embryoid body (EB) formation [24, 44]. Direct differentiation on monolayers of human fibroblast ensures more consistent differentiation results compared with EB formation [20].…”

Section: Stem Cells Are Novel and Unlimited Source For Male Gametementioning

confidence: 99%

Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

Volarević

Bojić

Nurković

et al. 2014

BioMed Research International

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Stem cells are undifferentiated cells that are present in the embryonic, fetal, and adult stages of life and give rise to differentiated cells that make up the building blocks of tissue and organs. Due to their unlimited source and high differentiation potential, stem cells are considered as potentially new therapeutic agents for the treatment of infertility. Stem cells could be stimulated in vitro to develop various numbers of specialized cells including male and female gametes suggesting their potential use in reproductive medicine. During past few years a considerable progress in the derivation of male germ cells from pluripotent stem cells has been made. In addition, stem cell-based strategies for ovarian regeneration and oocyte production have been proposed as future clinical therapies for treating infertility in women. In this review, we summarized current knowledge and present future perspectives and challenges regarding the use of stem cells in reproductive medicine.

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Germ‐like cell differentiation from induced pluripotent stem cells (iPSCs)

Niu

Chu

et al. 2012

Cell Biochemistry & Function

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Copyright: Sato et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Cervical reserve cells are epithelial progenitor cells that are pathologically evident as the origin of cervical cancer. Thus, investigating the characteristics of cervical reserve cells could yield insight into the features of cervical cancer stem cells (CSCs). In this study, we established a method for the regeneration of cervical reserve cell-like properties from human induced pluripotent stem cells (iPSCs) and named these cells induced reserve cell-like cells (iRCs). Approximately 70% of iRCs were positive for the reserve cell markers p63, CK5 and CK8. iRCs also expressed the SC junction markers CK7, AGR2, CD63, MMP7 and GDA. While iRCs expressed neither ERα nor ERβ, they expressed CA125. These data indicated that iRCs possessed characteristics of cervical epithelial progenitor cells. iRCs secreted higher levels of several inflammatory cytokines such as macrophage migration inhibitory factor (MIF), soluble intercellular adhesion molecule 1 (sICAM-1) and C-X-C motif ligand 10 (CXCL-10) compared with normal cervical epithelial cells. iRCs also expressed human leukocyte antigen-G (HLA-G), which is an important cell-surface antigen for immune tolerance and carcinogenesis. Together with the fact that cervical CSCs can originate from reserve cells, our data suggested that iRCs were potent immune modulators that might favor cervical cancer cell survival. In conclusion, by generating reserve cell-like properties from iPSCs, we provide a new approach that may yield new insight into cervical cancer stem cells and help find new oncogenic targets.

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Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules

Cited by 56 publications

References 40 publications

VEGF/VEGFR<sub>2</sub> Signaling Regulates Germ Cell Proliferation in vitro<b> </b>and Promotes Mouse Testicular Regeneration in vivo

VEGF/VEGFR<sub>2</sub> Signaling Regulates Germ Cell Proliferation in vitro<b> </b>and Promotes Mouse Testicular Regeneration in vivo

Stem Cells as New Agents for the Treatment of Infertility: Current and Future Perspectives and Challenges

Germ‐like cell differentiation from induced pluripotent stem cells (iPSCs)

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