ArticleStem cell research & therapy2020
A cytokine screen using CRISPR-Cas9 knock-in reporter pig iPS cells reveals that Activin A regulates NANOG.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 12 citations in OpenAlex.
- Signaling Pathways in Human Blastocyst Development: From Molecular Mechanisms to In Vitro Optimization.Journal of developmental biology · 2025Review
- The progress of induced pluripotent stem cells derived from pigs: a mini review of recent advances.Frontiers in cell and developmental biology · 2024Review
- Generation and characterization of stable pig pregastrulation epiblast stem cell lines.Cell research · 2022Article
- Comparative assessment of the cell-surface antigens and gene expression profiles of the gingival tissue biomarkers in subjects with fixed functional and removable functional orthodontic appliances.Saudi journal of biological sciences · 2022Article
- Article
- SOX2, OCT4 and NANOG: The core embryonic stem cell pluripotency regulators in oral carcinogenesis.Journal of oral and maxillofacial pathology : JOMFPReview
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
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Abstract
backgroundNANOG functions as the gateway for the generation of pluripotent stem cells (PSCs) in mice and humans. NANOG is a transcription factor highly expressed in pig pre-implantation embryos, indicating that it is a conserved pluripotency-associated factor. However, pig NANOG reporter PSCs have yet to be established, and the regulation of pluripotency by NANOG is not fully understood in this animal.
methodsIn this study, pig NANOG tdTomato knock-in reporter positive PC-iPS cells were established using CRISPR/Cas9. The resulting cell line was treated with several cytokines and their corresponding inhibitors to identify pathways that regulate NANOG expression. The pathways examined were LIF (leukemia inhibitory factor)/IL6 (interleukin 6)-STAT3, FGF (fibroblast growth factor)/ERK, IGF1 (insulin-like growth factor 1)/PIP3 (phosphoinositide 3-kinase)-AKT, Activin A/SMAD, and BMP4 (bone morphogenetic proteins)/SMAD.
resultsOur experiments showed that the Activin A/SMAD pathway is directly associated with activation of NANOG expression in the pig, as is also the case in mice and humans. Activin A directly regulates the expression of pig NANOG via SMAD2/3; inhibition of this pathway by SB431542 resulted in inhibition of NANOG expression.
conclusionsOur results show that Activin A plays an important regulatory role in NANOG-mediated pluripotency in pig iPS cells. Activin A treatment may be therefore an effective method for de novo derivation of authentic embryonic stem cells (ESCs) from pig pre-implantation embryos.
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