miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions

Ishikawa, Daichi; Diekmann, Ulf; Fiedler, Jan; Just, Annette; Thum, Thomas; Lenzen, Sigurd; Naujok, Ortwin

doi:10.1016/j.stemcr.2017.10.011

Cited by 26 publications

(21 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, CXCR4 − cells expressed similar levels of POU5F1 , SOX2 and NANOG as undifferentiated hESCs without significant inductions of differentiation markers (Figs 4E and S2). In line with our recent publication 30 , this indicates that the CXCR4 − population comprised cells that resisted differentiation.…”

Section: Resultssupporting

confidence: 90%

“…( F ) Gene expression changes of HNF6 , SOX9 , PDX1 , HNF1B , FOXA2 and NKX6 . 1 upon differentiation of DE clusters obtained by XF-3D according to the Kieffer-protocol 30 . Values are means ± SEM n = 3.…”

Section: Resultsmentioning

confidence: 99%

“…HESC lines HES3 and HUES8 and the hiPSC line hCBiPSC2 51 were cultivated as described earlier 4,27,30 . Briefly, all hPSCs were cultured as colonies on cell culture plastic coated with hESC-qualified Matrigel (Corning, Amsterdam, Netherlands).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Chemically defined and xenogeneic-free differentiation of human pluripotent stem cells into definitive endoderm in 3D culture

Diekmann

Wolling

Dettmer

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

In vitro differentiation of human pluripotent stem cells (hPSCs) into definitive endoderm (DE) represents a key step towards somatic cells of lung, liver and pancreas. For future clinical applications, mass production of differentiated cells at chemically defined conditions and free of xenogeneic substances is envisioned. In this study we adapted our previously published two-dimensional (2D) DE induction protocol to three-dimensional (3D) static suspension culture in the absence of the xenogeneic extracellular matrix Matrigel. Next, fetal calf serum and bovine serum albumin present in the standard medium were replaced by a custom-made and xeno-free B-27. This yielded in a chemically defined and xenogeneic-free 3D culture protocol for differentiation of hPSCs into DE at efficiencies similar to standard 2D conditions. This novel protocol successfully worked with different hPSC lines including hESCs and hiPSCs maintained in two different stem cell media prior to differentiation. DE cells obtained by our novel BSA-free 3D protocol could be further differentiated into PDX1- or NKX6.1-expressing pancreatic progenitor cells. Notably, upon DE differentiation, we also identified a CXCR4+/NCAM+/EpCAMlow cell population with reduced DE marker gene expression. These CXCR4+/NCAM+/EpCAMlow cells emerge as a result of Wnt/beta-catenin hyperactivation via elevated CHIR-99021 concentrations and likely represent misspecified DE.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Chemically defined and xenogeneic-free differentiation of human pluripotent stem cells into definitive endoderm in 3D culture

Diekmann

Wolling

Dettmer

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Exogenous addition of miR-489-3p significantly reduced the expression of its target gene MEK1 in normal cells (Kuppa et al, 2018). When endoderm-specific miR-489-3p was overexpressed in human embryonic stem cells, endoderm differentiation was accelerated and increased (Ishikawa et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

miR-489-3p Regulates the Oxidative Stress Response in the Liver and Gill Tissues of Hybrid Yellow Catfish (Pelteobagrus fulvidraco♀ × P. vachelli♂) Under Cu2+ Exposure by Targeting Cu/Zn-SOD

et al. 2019

View full text Add to dashboard Cite

Copper/zinc superoxide dismutase (Cu/Zn-SOD) plays critical roles in protecting cells and tissues against oxidative damage. Excessive copper ions (Cu 2+ ) in water can damage the cells of aquatic organisms, leading to impaired growth and development and reduced antioxidant defenses. Many regulatory factors control the response to excess Cu 2+ . Among them, microRNAs (miRNAs) are important small RNAs that regulate the expression of their target genes and participate in the oxidative stress response. In the present study, we used bioinformatics and dual luciferase reporter gene analyses to demonstrate that the miR-489-3p of hybrid yellow catfish ( Pelteobagrus fulvidraco ♀ × P. vachelli ♂) binds to the 3′-untranslated region (UTR) of its target gene, which encodes a Cu/Zn-SOD. The regulatory relationship between this miRNA and its target gene Cu/Zn-SOD was analyzed using qRT-PCR and luciferase activity assays. We also investigated the effect of the loss of miR-489-3p expression on the oxidative stress response of hybrid yellow catfish exposed to Cu 2+ . The Cu/Zn-SOD 3′UTR region was found to be fully complementary to positions 2–9 of the 5′-end seed region of miR-489-3p. The miR-489-3p expression levels were negatively related to Cu/Zn-SOD expression. Silencing of miR-489-3p up-regulated Cu/Zn-SOD expression in the liver and gill tissues, increased activities of SOD and catalase, and reduced the malondialdehyde content. This study is the first to demonstrate that miR-489-3p targets Cu/Zn-SOD to mediate the oxidative response to metal stress. These findings provide a theoretical basis for further studies on the response to oxidative stress caused by metals in cultured fish, and provide an experimental basis for the management of the culture environment.

show abstract

“…Mesoderm cells showed enrichment of miR-483-3p that was identified as a pivotal regulator for the differentiation to progenitor subpopulations toward lineage specification. MiR-483-3p effect was partially mimicked by repression of its target PGAM1 gene [ 39 ].…”

Section: Physiological Roles Of Mir-483-3pmentioning

confidence: 99%

The Glucose-Regulated MiR-483-3p Influences Key Signaling Pathways in Cancer

Pepe

Visone

Veronese

2018

Cancers

View full text Add to dashboard Cite

The hsa-mir-483 gene, located within the IGF2 locus, transcribes for two mature microRNAs, miR-483-5p and miR-483-3p. This gene, whose regulation is mediated by the the CTNNB1/USF1 complex, shows an independent expression from its host gene IGF2. The miR-483-3p affects the Wnt/β-catenin, the TGF-β, and the TP53 signaling pathways by targeting several genes as CTNNB1, SMAD4, IGF1, and BBC3. Accordingly, miR-483-3p is associated with various tissues specific physiological properties as insulin and melanin production, as well as with cellular physiological functions such as wounding, differentiation, proliferation, and survival. Deregulation of miR-483-3p is observed in different types of cancer, and its overexpression can inhibit the pro-apoptotic pathway induced by the TP53 target effectors. As a result, the oncogenic characteristics of miR-483-3p are linked to the effect of some of the most relevant cancer-related genes, TP53 and CTNNB1, as well as to one of the most important cancer hallmark: the aberrant glucose metabolism of tumor cells. In this review, we summarize the recent findings regarding the miR-483-3p, to elucidate its functional role in physiological and pathological contexts, focusing overall on its involvement in cancer and in the TP53 pathway.

show abstract

miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions

Cited by 26 publications

References 40 publications

Chemically defined and xenogeneic-free differentiation of human pluripotent stem cells into definitive endoderm in 3D culture

Chemically defined and xenogeneic-free differentiation of human pluripotent stem cells into definitive endoderm in 3D culture

miR-489-3p Regulates the Oxidative Stress Response in the Liver and Gill Tissues of Hybrid Yellow Catfish (Pelteobagrus fulvidraco♀ × P. vachelli♂) Under Cu2+ Exposure by Targeting Cu/Zn-SOD

The Glucose-Regulated MiR-483-3p Influences Key Signaling Pathways in Cancer

Contact Info

Product

Resources

About