ArticleCell communication and signaling : CCS2013
Direct transdifferentiation of spermatogonial stem cells to morphological, phenotypic and functional hepatocyte-like cells via the ERK1/2 and Smad2/3 signaling pathways and the inactivation of cyclin A, cyclin B and cyclin E.
Article in Cell communication and signaling : CCS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Expansion and long-term culture of human spermatogonial stem cells via the activation of SMAD3 and AKT pathways.Experimental biology and medicine (Maywood, N.J.) · 2015Trial
- Multi-omic analysis of androgen-deprived human testes reveals Sertoli cell regulation and niche reprogramming.Nature communications · 2026Article
- High-content analysis of testicular toxicity of BPA and its selected analogs in mouse spermatogonial, Sertoli cells, and Leydig cells revealed BPAF induced unique multinucleation phenotype associated with the increased DNA synthesis.Toxicology in vitro : an international journal published in association with BIBRA · 2023Article
- OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility.Research (Washington, D.C.) · 2023Article
- GPx3 knockdown inhibits the proliferation and DNA synthesis and enhances the early apoptosis of human spermatogonial stem cells via mediating CXCL10 and cyclin B1.Frontiers in cell and developmental biology · 2023Article
- Spermatogonial stem-cell-derived neural-like cell transplantation enhances the functional recovery of a rat spinal cord injury model: characterization of evoked potentials.Frontiers in neuroscience · 2023Article
- The PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?Histology and histopathology · 2022Review
- Functions of somatic cells for spermatogenesis in stallions.Journal of animal science and technology · 2022Review
- Article
- Parabolic relationship betweenFrontiers in cell and developmental biology · 2022Article
- Liver Regeneration and Cell Transplantation for End-Stage Liver Disease.Biomolecules · 2021Review
- Article
- Spermatogonial stem cells are a promising and pluripotent cell source for regenerative medicine.American journal of translational research · 2020Review
- Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes.Stem cell research & therapy · 2019Article
- MiR-663a Stimulates Proliferation and Suppresses Early Apoptosis of Human Spermatogonial Stem Cells by Targeting NFIX and Regulating Cell Cycle.Molecular therapy. Nucleic acids · 2018Article
- PAK1 Promotes the Proliferation and Inhibits Apoptosis of Human Spermatogonial Stem Cells via PDK1/KDR/ZNF367 and ERK1/2 and AKT Pathways.Molecular therapy. Nucleic acids · 2018Article
- From the Cover: An Animal-Free In Vitro Three-Dimensional Testicular Cell Coculture Model for Evaluating Male Reproductive Toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Transdifferentiation of human male germline stem cells to hepatocytes in vivo via the transplantation under renal capsules.Oncotarget · 2017Article
- High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells.Molecular neurobiology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere shortage of liver donors and hepatocytes highlights urgent requirement of extra-liver and stem cell source of hepatocytes for treating liver-related diseases. Here we hypothesized that spermatogonial stem cells (SSCs) can directly transdifferentiate to hepatic stem-like cells capable of differentiating into mature hepatocyte-like cells in vitro without an intervening pluripotent state.
resultsSSCs first changed into hepatic stem-like cells since they resembled hepatic oval cells in morphology and expressed Ck8, Ck18, Ck7, Ck19, OV6, and albumin. Importantly, they co-expressed CK8 and CK19 but not ES cell markers. Hepatic stem-like cells derived from SSCs could differentiate into small hepatocytes based upon their morphological features and expression of numerous hepatic cell markers but lacking of bile epithelial cell hallmarks. Small hepatocytes were further coaxed to differentiate into mature hepatocyte-like cells, as identified by their morphological traits and strong expression of Ck8, Ck18, Cyp7a1, Hnf3b, Alb, Tat, Ttr, albumin, and CYP1A2 but not Ck7 or CK19. Notably, these differentiated cells acquired functional attributes of hepatocyte-like cells because they secreted albumin, synthesized urea, and uptake and released indocyanine green. Moreover, phosphorylation of ERK1/2 and Smad2/3 rather than Akt was activated in hepatic stem cells and mature hepatocytes. Additionally, cyclin A, cyclin B and cyclin E transcripts and proteins but not cyclin D1 or CDK1 and CDK2 transcripts or proteins were reduced in mature hepatocyte-like cells or hepatic stem-like cells derived from SSCs compared to SSCs.
conclusionsSSCs can transdifferentiate to hepatic stem-like cells capable of differentiating into cells with morphological, phenotypic and functional characteristics of mature hepatocytes via the activation of ERK1/2 and Smad2/3 signaling pathways and the inactivation of cyclin A, cyclin B and cyclin E. This study thus provides an invaluable source of mature hepatocytes for treating liver-related diseases and drug toxicity screening and offers novel insights into mechanisms of liver development and cell reprogramming.
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