ArticleStem cell research & therapy2021
Valproic acid promotes the in vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Artificial Gametogenesis and In Vitro Spermatogenesis: Emerging Strategies for the Treatment of Male Infertility.International journal of molecular sciences · 2025Review
- 3D Bioprinted Coaxial Testis Model Using Human Induced Pluripotent Stem Cells:A Step Toward Bicompartmental Cytoarchitecture and Functionalization.Advanced healthcare materials · 2025Article
- Endocannabinoid system upregulates the enrichment and differentiation of human iPSC- derived spermatogonial stem cells via CB2R agonism.Biological research · 2025Article
- Analysis of ASMs and male infertility using the FDA adverse event reporting system (FAERS).Frontiers in public health · 2025Article
- The Evolutionary Route of in vitro Human Spermatogenesis: What is the Next Destination?Stem cell reviews and reports · 2024Review
- Palmitoylation of vacuole membrane protein 1 promotes small extracellular vesicle secretion via interaction with ALIX and influences intercellular communication.Cell communication and signaling : CCS · 2024Article
- RNA mCellular and molecular life sciences : CMLS · 2024Article
- Identification and validation of SHC1 and FGFR1 as novel immune-related oxidative stress biomarkers of non-obstructive azoospermia.Frontiers in endocrinology · 2024Article
- Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.World journal of stem cells · 2023Article
- Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway.BMC neuroscience · 2023Article
- Sertoli cell-only syndrome: advances, challenges, and perspectives in genetics and mechanisms.Cellular and molecular life sciences : CMLS · 2023Review
- Single-cell multi-omics analysis reveals dysfunctional Wnt signaling of spermatogonia in non-obstructive azoospermia.Frontiers in endocrinology · 2023Article
- A homozygous PIWIL2 frameshift variant affects the formation and maintenance of human-induced pluripotent stem cell-derived spermatogonial stem cells and causes Sertoli cell-only syndrome.Stem cell research & therapy · 2022Article
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6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundStudying human germ cell development and male infertility is heavily relied on mouse models. In vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells (SSCLCs) can be used as a model to study human germ cells and infertility. The current study aimed to develop the SSCLC induction protocol and assess the effects of the developed protocol on SSCLC induction.
methodsWe examined the effects of valproic acid (VPA), vitamin C (VC) and the combination of VPA and VC on the SSCLC induction efficiency and determined the expression of spermatogonial genes of differentiated cells. Haploid cells and cells expressed meiotic genes were also detected. RNA-seq analysis was performed to compare the transcriptome between cells at 0 and 12 days of differentiation and differently expressed genes were confirmed by RT-qPCR. We further evaluated the alteration in histone marks (H3K9ac and H3K27me3) at 12 days of differentiation. Moreover, the SSCLC induction efficiency of two hiPSC lines of non-obstructive azoospermia (NOA) patients was assessed using different induction protocols.
resultsThe combination of low concentrations of VPA and VC in the induction medium was most effective to induce SSCLCs expressing several spermatogonial genes from human pluripotent stem cells at 12 days of differentiation. The high concentration of VPA was more effective to induce cells expressing meiotic genes and haploid cells. RNA-seq analysis revealed that the induction of SSCLC involved the upregulated genes in Wnt signaling pathway, and cells at 12 days of differentiation showed increased H3K9ac and decreased H3K27me3. Additionally, two hiPSC lines of NOA patients showed low SSCLC induction efficiency and decreased expression of genes in Wnt signaling pathway.
conclusionsVPA robustly promoted the differentiation of human pluripotent stem cells into SSCLCs, which involved the upregulated genes in Wnt signaling pathway and epigenetic changes. hiPSCs from NOA patients showed decreased SSCLC induction efficiency and Wnt signaling pathway gene expression, suggesting that SSC depletion in azoospermia testes might be associated with inactivation of Wnt signaling pathway. Our developed SSCLC induction protocol provides a reliable tool and model to study human germ cell development and male infertility.
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