In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells

Jung, Dajung; Xiong, Jingang; Ye, Min; Qin, Xu‐Jie; Lin, Li; Cheng, Shun‐Feng; Luo, Maohui; Jia, Peng; Dong, Ji; Tang, Fuchou; Shen, Wei; Matzuk, Martin M.; Kee, Kehkooi

doi:10.1038/ncomms15680

Cited by 97 publications

(99 citation statements)

References 45 publications

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“…Quantitative real‐time PCR (q‐PCR) analysis was carried out as previously described (Jung et al., ). The specific primers used in q‐PCR analysis are listed in Table S3.…”

Section: Methodsmentioning

confidence: 99%

DNAH6is a novel candidate gene associated with sperm head anomaly

Sha

et al. 2018

Andrologia

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Globozoospermia and acephalic spermatozoa are two rare sperm head anomalies associated with male infertility. Combination of the two phenotypes in the same patient is extremely rare, so the underlying pathogenesis of this disorder remains unclear. Here, we report a 35-year-old infertile male, who presented with 30% of sperm-lacked heads and 69% of sperm round-headed or small-headed with neck thickening in his ejaculate. Subsequent whole-exome sequencing (WES) analysis identified compound heterozygous variants within the DNAH6 gene. DNAH6 is a testis-specific-expressed protein that was localised to the neck region in the spermatozoa of normal control; however, immunofluorescent staining failed to detect DNAH6 protein in the patient's spermatozoa. Quantitative real-time PCR analysis also showed the complete absence of DNAH6 mRNA in the patient's spermatozoa. Moreover, two cycles of in vitro fertilisation (IVF)-assisted reproduction were carried out, but pregnancy was not achieved after embryo transfer. Therefore, rare sequence variants in DNAH6 might be susceptibility risks for human sperm head anomaly.

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“…Quantitative real‐time PCR (q‐PCR) analysis was carried out as previously described (Jung et al., ). The specific primers used in q‐PCR analysis are listed in Table S3.…”

Section: Methodsmentioning

confidence: 99%

DNAH6is a novel candidate gene associated with sperm head anomaly

Sha

et al. 2018

Andrologia

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“…We examined the ability of hiSCs to sustain mouse spermatogonia cells because of the inaccessible procurement of human spermatogonia cells from hospitals. Previous studies performing xenotransplantation experiments transplanting primate spermatogonia stem cells into mouse testis demonstrated that primate germ cells colonized in the seminiferous tubules of the recipient mice, but the primate germ cells did not differentiate because of the evolutionary differences between these species 50 . The isolated mouse spermatogonia cells in our study attached and survived on the hiSCs, but no differentiated spermatocytes were detected (Fig.…”

Section: Discussionmentioning

confidence: 99%

Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4

Liang

Wang

et al. 2018

Preprint

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Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). The induction of human Sertoli cells from fibroblasts could provide cellular sources for fertility and transplantation treatments. Here, we report the in vitro reprogramming of human fibroblasts to Sertoli cells and characterize these human induced Sertoli cells (hiSCs). Initially, five transcriptional factors (NR5A1, GATA4, WT1, SOX9 and DMRT1) and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, i.e., NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles that are similar to those of primary human Sertoli cells. Consistent with the known cellular properties of Sertoli cells, hiSCs attract endothelial cells and exhibit high number of lipid droplets in the cytoplasm. More importantly, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. In addition, hiSCs suppress the production of IL-2 and proliferation of human T lymphocytes. When hiSCs were cotransplanted with human embryonic kidney cells, these xenotransplanted human cells survived longer in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli-only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.

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“…195 However, with regard to hESCs, development of structures resembling primary ovarian follicles was the most advanced stage of differentiation that could be reached. 196…”

Section: Generation Of Oocytes From Embryonic and Induced Pluripotentmentioning

confidence: 99%

<p>Role of stem cells in fertility preservation: current insights</p>

Vermeulen¹,

Giudice²,

Vento³

et al. 2019

SCCAA

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While improvements made in the field of cancer therapy allow high survival rates, gonadotoxicity of chemo- and radiotherapy can lead to infertility in male and female pre- and postpubertal patients. Clinical options to preserve fertility before starting gonadotoxic therapies by cryopreserving sperm or oocytes for future use with assisted reproductive technology (ART) are now applied worldwide. Cryopreservation of pre- and postpubertal ovarian tissue containing primordial follicles, though still considered experimental, has already led to the birth of healthy babies after autotransplantation and is performed in an increasing number of centers. For prepubertal boys who do not produce gametes ready for fertilization, cryopreservation of immature testicular tissue (ITT) containing spermatogonial stem cells may be proposed as an experimental strategy with the aim of restoring fertility. Based on achievements in nonhuman primates, autotransplantation of ITT or testicular cell suspensions appears promising to restore fertility of young cancer survivors. So far, whether in two- or three-dimensional culture systems, in vitro maturation of immature male and female gonadal cells or tissue has not demonstrated a capacity to produce safe gametes for ART. Recently, primordial germ cells have been generated from embryonic and induced pluripotent stem cells, but further investigations regarding efficiency and safety are needed. Transplantation of mesenchymal stem cells to improve the vascularization of gonadal tissue grafts, increase the colonization of transplanted cells, and restore the damaged somatic compartment could overcome the current limitations encountered with transplantation.

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In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells

Cited by 97 publications

References 45 publications

DNAH6is a novel candidate gene associated with sperm head anomaly

DNAH6is a novel candidate gene associated with sperm head anomaly

Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4

<p>Role of stem cells in fertility preservation: current insights</p>

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