Sox2, a key factor in the regulation of pluripotency and neural differentiation

Zhang, Shuchen; Cui, Wei

doi:10.4252/wjsc.v6.i3.305

Cited by 327 publications

(265 citation statements)

References 52 publications

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“…Interestingly, while the expression of swine endogenous OCT4, KLF4 and NANOG was downregulated 4 days after doxycycline withdrawal, the expression of swine endogenous SOX2 and c-MYC appeared to be upregulated (Supplementary Fig. 5A), possibly due to the induction of early neuroectodermal/progenitor lineage that may maintain a high expression level of SOX2 and c-MYC[23, 24]. Notably, a marked reduction of all five swine endogenous pluripotency markers including SOX2 and c-MYC was observed upon a 12-day spontaneous differentiation of siPSCs in the absence of doxycycline and self-renewal growth factors (LIF and bFGF) (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

et al. 2017

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Development of autologous tissue-engineered vascular constructs using vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (iPSCs) holds great potential in treating patients with vascular disease. However, preclinical, large animal iPSC-based cellular and tissue models are required to evaluate safety and efficacy prior to clinical application. Herein, swine iPSC (siPSC) lines were established by introducing doxycycline-inducible reprogramming factors into fetal fibroblasts from a line of inbred Massachusetts General Hospital miniature swine that accept tissue and organ transplants without immunosuppression within the line. Highly enriched, functional VSMCs were derived from siPSCs based on addition of ascorbic acid and inactivation of reprogramming factor via doxycycline withdrawal. Moreover, siPSC-VSMCs seeded onto biodegradable polyglycolic acid (PGA) scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of the mature VSMC marker, smooth muscle myosin heavy chain. Finally, using a robust cellular self-assembly approach, we developed 3D scaffold-free tissue rings from siPSC-VSMCs that showed comparable mechanical properties and contractile function to those developed from swine primary VSMCs. These engineered vascular constructs, prepared from doxycycline-inducible inbred siPSCs, offer new opportunities for preclinical investigation of autologous human iPSC-based vascular tissues for patient treatment.

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Section: Resultsmentioning

confidence: 99%

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

et al. 2017

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“…Thus, in this study, we also investigated the expression of pluripotent genes such as OCT4, Nanog and Sox2 because canine embryonic stem cells were demonstrated to express Oct4, Nanog, and Sox2 at high levels [38] . Sox2 governs ESC specification to neuroectoderm while Oct4 and Nanog promote their differentiation to mesendoderm, a common precursor of mesoderm and definitive endoderm [39] , and Sox2 is a critical factor for directing the differentiation of pluripotent stem cells to neural progenitors and for maintaining the properties of neural progenitor stem cells [40] . In this study, we observed expressions of these pluripotent genes in OS cells and detected the downregulation of Nanog, Oct4 and the upregulation of Sox2 ALTUNBAŞ, YAPRAKÇI ÇELİK in the NSs derived from OS cells.…”

Section: Discussionmentioning

confidence: 99%

Köpek Olfaktorik Mukozasindan Olfaktorik Kök Hücrelerin Izolasyonu ve Karakterizasyonu

Altunbaş¹,

Yaprakci²,

Çeli̇k³

2015

Kafkas Univ Vet Fak Derg

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Olfactory stem cells have great potential in the treatment of neurodegenerative diseases and they are good candidates for cell therapy due to the easy accessibility of olfactory mucosa. The main objectives of this study were isolation, proliferation and characterization of olfactory mucosa stem cells that were further differentiated into olfactory neurospheres derived cells. When grown on poly-Dlysine with a serum-free culture medium supplemented with EGF (50 ng/ml) and FGF2 (50 ng/ml), olfactory stem cells gave rise to neurospheres. When grown in serum-containing culture medium newly plated spheres gave rise to olfactory neurosphere derived cells. Gene expression analysis revealed that, OCT4, SOX2, Nanog, Nestin, β-tubulin and NCAM were expressed in olfactory stem cells. While the mRNA expressions of Nanog, Nestin, Oct4, βIII-tubulin and NCAM were downregulated in neurospheres, the mRNA expression of SOX2 upregulated in neurospheres. According to the gene levels of neurospheres generated from olfactory stem cells, beta tubulin and NCAM gene expressions were upregulated, whereas OCT4, Nanog, Sox2 and Nestin mRNA expressions were downregulated in Olfactory neurospheres derived cells. Olfactory mucosa of canine is a suitable alternative source of stem cells and can be applied to cell therapy in neurodegenerative diseases. Keywords: Olfactory stem cell, Canine, Neurosphere, Pluripotent Köpek Olfaktorik Mukozasindan Olfaktorik Kök Hücrelerin Izolasyonu ve Karakterizasyonu ÖzetOlfaktorik kök hücreler nörodejeneratif hastalıkların tedavisinde büyük bir potansiyele sahiptir ve olfaktorik mukozaya kolay erişilebilirliği sayesinde hücre tedavisi için uygun bir adaydır. Bu çalışmanın amacı olfaktorik nörosfer kaynaklı hücrelere kadar farklılaştırılabilen olfaktorik kök hücrelerin izolasyonu, proliferasyonu ve karakterizasyonudur. Olfaktorik kök hücreler EGF (50 ng/ml) ve FGF (50 ng/ml) içeren serumsuz kültür vasatı içerisinde kültüre edildiğinde nörosferleri oluşturdular. Serum içeren kültür vasatında tekrar kültüre edildiklerinde olfaktorik nörosfer kaynaklı hücreleri şekillendirdiler. Gen ekspresyon analizleri OCT4, SOX2, Nanog, Nestin, β-tubulin ve NCAM genlerinin olfaktorik kök hücrelerinde eksprese olduğunu ortaya çıkardı. Nanog, Nestin, Oct4, β tubulin ve NCAM gen ekspresyonları nörosferlerde downregüle olurken, SOX2 geni upregüle oldu. Olfaktorik kök hücrelerin oluşturduğu nörosferlerin gen seviyeleri ile karşılaştırıldığında olfaktorik nörosfer kaynaklı hücrelerde β tubulin ve NCAM gen ekspresyonları upregüle olurken OCT4, Nanog, Sox2 and Nestin mRNA ekspresyonları downregüle oldu. Köpeğin olfaktorik mukozası uygun alternatif bir kök hücre kaynağıdır ve köpek nörodejeneratif hastalıklarında hücre tedavisi için uygulanabilir.

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“…For example, C44 is highly active in ESC and remains active at later stages in all 4 brain tissues, suggesting its critical role in the regulation of pluripotency and neural differentiation. Indeed, Sox2 from C44 has been demonstrated to be a pluripotency factor and play a pivotal role in neural differentiation 23 . Similar to C44, C6 also exhibits ectoderm-specific pattern from E10.5 to P0.…”

Section: Transcriptional Waves During Embryogenesismentioning

confidence: 99%

Systems-level identification of transcription factors critical for mouse embryonic development

Zhang

Wang

Zhao

et al. 2017

Preprint

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Dynamic changes in the transcriptional regulatory circuit can influence the specification of distinct cell types. Numerous transcription factors (TFs) have been shown to function through dynamic rewiring during embryonic development but a comprehensive survey on the global regulatory network is still lacking. Here, we performed an integrated analysis of epigenomic and transcriptomic data to reveal key regulators from 2 cells to postnatal day 0 in mouse embryogenesis. We predicted 3D chromatin interactions including enhancer-promoter interactions in 12 tissues across 8 developmental stages, which facilitates linking TFs to their target genes for constructing genetic networks. To identify driver TFs particularly those not necessarily differentially expressed ones, we developed a new algorithm, dubbed as Taiji, to assess the global importance of TFs in development. Through comparative analysis across tissues and developmental stages, we systematically uncovered TFs that are critical for lineage-specific and stage-dependent tissue specification. Most interestingly, we have identified TF combinations that function in spatiotemporal order to form transcriptional waves regulating developmental progress and differentiation. Not only does our analysis provide the first comprehensive map of transcriptional regulatory circuits during mouse embryonic development, the identified novel regulators and the predicted 3D chromatin interactions also provide a valuable resource to guide further mechanistic studies.

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Sox2, a key factor in the regulation of pluripotency and neural differentiation

Cited by 327 publications

References 52 publications

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering

Köpek Olfaktorik Mukozasindan Olfaktorik Kök Hücrelerin Izolasyonu ve Karakterizasyonu

Systems-level identification of transcription factors critical for mouse embryonic development

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