IWP 2
Chemical Name: N-(6-Methyl-2-benzothiazolyl)-2-[(3,4,6,7-tetrahydro-4-oxo-3-phenylthieno[3,2-d]pyrimidin-2-yl)thio]-acetamide
Purity: ≥98%
Biological Activity
IWP 2 is a potent inhibitor of Wnt processing and secretion (IC50 = 27nM). IWP 2 inactivates PORCN, a membrane-bound O-acyltransferase (MBOAT), and selectively inhibits palmitoylation of Wnt. Blocks Wnt-dependent phosphorylation of Lrp6 receptor and Dvl2, and β-catenin accumulation. IWP 2 suppresses self-renewal in R1 embryonic stem cells and promotes cardiomyocyte differentiation from hPSCs. The compound has also been used in protocols to reprogram human somatic cells to chemically-induced PSCs.Scientific Data
iPSC-derived Human Heart-forming Organoids Human iPSCs were embedded in Cultrex™ UltiMatrix RGF Basement Membrane Extract (R&D Systems, Catalog # BME001-05) and differentiated with CHIR 99021 (Tocris Bioscience, Catalog # TB4423-GMP) and IWP 2 (Tocris Bioscience, Catalog # 3533) into heart-forming organoids based on a protocol from Drakhlis, L. et al. (2021) Nat. Biotechnol. 39:737. Successful differentiation was demonstrated by staining the cells with A) a Rabbit Anti-Human Cardiac Troponin T Antigen Affinity-purified Polyclonal Antibody (green; Novus Biologicals, Catalog # NBP3-13391) to detect cardiomyocytes and a Goat Anti-Human CD31/PECAM-1 Antigen Affinity-purified Polyclonal Antibody (red; R&D Systems, Catalog # AF3628) to detect endothelial cells. The cells were counterstained with DAPI (blue; Tocris Bioscience, Catalog # 5748). As formation of early embryonic heart anlagen is associated with nascent foregut endoderm development, cells were also stained with B) a Goat Anti-Human SOX2 Antigen Affinity-purified Polyclonal Antibody (red; R&D Systems, Catalog # AF2018) and a Mouse Anti-Human HNF-4 alpha/NR2A1 Monoclonal Antibody (green; R&D Systems, Catalog # PP-K9218-00) to detect anterior and posterior foregut endoderm cells, respectively. The cells were counterstained with DAPI (blue; Tocris Bioscience, Catalog # 5748).
Technical Data
The technical data provided above is for guidance only.
For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
Background References
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3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling
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Differential Sarcomere and Electrophysiological Maturation of Human iPSC-Derived Cardiac Myocytes in Monolayer vs. Aggregation-Based Differentiation Protocols
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Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes
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Product Datasheets
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Citations for IWP 2
The citations listed below are publications that use Tocris products. Selected citations for IWP 2 include:
102 Citations: Showing 1 - 10
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Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs.
Authors: Jing Et al.
NPJ Regen Med 2023;8:26
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Systematic discovery of transcription factors that improve hPSC-derived cardiomyocyte maturation via temporal analysis of bioengineered cardiac tissues.
Authors: Aditya Et al.
APL Bioeng 2023;7:026109
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Reduced Cell-ECM Interactions in the EpiSC Colony Center Cause Heterogeneous Differentiation.
Authors: Arpan Et al.
Cells 2023;12
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A distal lung organoid model to study interstitial lung disease, viral infection and human lung development.
Authors: Nadine Et al.
Nat Protoc 2023;
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FUCCI-Based Live Imaging Platform Reveals Cell Cycle Dynamics and Identifies Pro-proliferative Compounds in Human iPSC-Derived Cardiomyocytes.
Authors: Olaf Et al.
Front Cardiovasc Med 2022;9:840147
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Differentiating Human Pluripotent Stem Cells to Cardiomyocytes Using Purified Extracellular Matrix Proteins.
Authors: Teisha J Et al.
Bioengineering (Basel) 2022;9
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Retrograde movements determine effective stem cell numbers in the intestine.
Authors: David J Et al.
Nature 2022;607:548-554
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Tomatidine-stimulated maturation of human embryonic stem cell-derived cardiomyocytes for modeling mitochondrial dysfunction.
Authors: Jae Boum Et al.
Exp Mol Med 2022;54:493-502
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Autologous humanized mouse models of iPSC-derived tumors enable characterization and modulation of cancer-immune cell interactions.
Authors: Benjamin Et al.
Cell Rep Methods 2022;2:100153
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Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor.
Authors: Gregory Et al.
iScience 2022;25:104297
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A dual SHOX2:GFP; MYH6:mCherry knockin hESC reporter line for derivation of human SAN-like cells.
Authors: Xiaolu Et al.
iScience 2022;25:104153
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In Vitro Generation of Heart Field Specific Cardiomyocytes.
Authors: Reza Et al.
Methods Mol Biol 2022;2429:257-267
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Effects of Hypocalcemic Vitamin D Analogs in the Expression of DNA Damage Induced in Minilungs from hESCs: Implications for Lung Fibrosis.
Authors: Alberto Et al.
Int J Mol Sci 2022;23
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The Human Induced Pluripotent Stem Cell Test as an Alternative Method for Embryotoxicity Testing.
Authors: Leo Et al.
Int J Mol Sci 2022;23
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A Bionic Testbed for Cardiac Ablation Tools.
Authors: Brenda M Et al.
Int J Mol Sci 2022;23
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Autophagy modulates cell fate decisions during lineage commitment.
Authors: Elisabeth Et al.
Autophagy 2022;18:1915-1931
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The Biphasic Effect of Retinoic Acid Signaling Pathway on the Biased Differentiation of Atrial-like and Sinoatrial Node-like Cells from hiPSC.
Authors: Feng Et al.
Int J Stem Cells 2022;15:247-257
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iPSCs derived from esophageal atresia patients reveal SOX2 dysregulation at the anterior foregut stage.
Authors: Martin A Et al.
Dis Model Mech 2022;15
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Isolation and characterization of human embryonic stem cell-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles.
Authors: Peng Et al.
Cardiovasc Res 2022;118:828-843
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Efficient differentiation of human primordial germ cells through geometric control reveals a key role for Nodal signaling.
Authors: Ran Et al.
Elife 2022;11
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An iPS-derived in vitro model of human atrial conduction.
Authors: Kentaro Et al.
Physiol Rep 2022;10:e15407
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Distinct properties of Ca2+ efflux from brain, heart and liver mitochondria: The effects of Na+, Li+ and the mitochondrial Na+/Ca2+ exchange inhibitor CGP37157.
Authors: Stefan Et al.
Cell Calcium 2021;96:102382
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Myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes.
Authors: Bin Et al.
Biochem Biophys Res Commun 2021;552:84-90
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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro.
Authors: Cecilia Et al.
Nat Genet 2021;53:1698-1711
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A simple protocol to produce mature human-induced pluripotent stem cell-derived cardiomyocytes.
Authors: Yingqiong Et al.
STAR Protoc 2021;2:100912
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Assessing the Wnt-reactivity of cytonemes of mouse embryonic stem cells using a bioengineering approach.
Authors: Shukry J Et al.
STAR Protoc 2021;2:100813
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Isolation of human ESC-derived cardiac derivatives and embryonic heart cells for population and single-cell RNA-seq analysis.
Authors: Kenneth R Et al.
STAR Protoc 2021;2:100339
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Principles of signaling pathway modulation for enhancing human naive pluripotency induction.
Authors: Varda Et al.
Cell Stem Cell 2021;28:1549-1565.e12
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Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids.
Authors: Ling Et al.
Cell Stem Cell 2021;28:1090-1104.e6
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Human Pluripotent Stem Cells for High-Throughput Drug Screening and Characterization of Small Molecules.
Authors: Ruili Et al.
Methods Mol Biol 2021;2454:811-827
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Identification of New Transcription Factors that Can Promote Pluripotent Reprogramming.
Authors: Duanqing Et al.
Stem Cell Rev Rep 2021;17:2223-2234
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Generation of heart-forming organoids from human pluripotent stem cells.
Authors: Robert Et al.
Nat Protoc 2021;16:5652-5672
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A microfluidics-based stem cell model of early post-implantation human development.
Authors: Jianping Et al.
Nat Protoc 2021;16:309-326
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The in vitro multilineage differentiation and maturation of lung and airway cells from human pluripotent stem cell-derived lung progenitors in 3D.
Authors: Matteo Et al.
Nat Protoc 2021;16:1802-1829
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p53 Promotes Differentiation of Cardiomyocytes from hiPSC through Wnt Signaling-Mediated Mesendodermal Differentiation.
Authors: Feng Et al.
Int J Stem Cells 2021;14:410-422
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Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells.
Authors: Sara Et al.
J Cardiovasc Thorac Res 2021;13:146-155
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QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function.
Authors: Ying Et al.
Nat Commun 2021;12:89
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Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity in vitro.
Authors: Arun Et al.
Cell Syst 2021;12:885-899.e8
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CRISPR/Cas9-mediated introduction of the sodium/iodide symporter gene enables noninvasive in?vivo tracking of induced pluripotent stem cell-derived cardiomyocytes.
Authors: Stefania Et al.
Stem Cells Transl Med 2020;9:1203-1217
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Cardiotoxicity induced by the combination therapy of chloroquine and azithromycin in human embryonic stem cell-derived cardiomyocytes.
Authors: Jae Ho Et al.
BMB Rep 2020;53:545-550
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Potently Cytotoxic Natural Killer Cells Initially Emerge from Erythro-Myeloid Progenitors during Mammalian Development.
Authors: Carissa Et al.
Dev Cell 2020;53:229-239.e7
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Generation of an INSULIN-H2B-Cherry reporter human iPSC line.
Authors: Ingo Et al.
Stem Cell Res 2020;45:101797
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Human Induced Pluripotent Stem Cell-Derived Non-Cardiomyocytes Modulate Cardiac Electrophysiological Maturation Through Connexin 43-Mediated Cell-Cell Interactions.
Authors: Timothy J Et al.
Stem Cells Dev 2020;29:75-89
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Naive Pluripotent Stem Cells Exhibit Phenotypic Variability that Is Driven by Genetic Variation.
Authors: Ludovic Et al.
Cell Stem Cell 2020;27:470-481.e6
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A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids
Authors: Yang Et al.
Cell Stem Cell 2020;27:125
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Protocol to Generate and Characterize Potent and Selective WNT Mimetic Molecules.
Authors: Hui Et al.
STAR Protoc 2020;1:100043
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Differentiation of PTH-Expressing Cells From Human Pluripotent Stem Cells.
Authors: Michael A Et al.
Endocrinology 2020;161
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Generation and trapping of a mesoderm biased state of human pluripotency.
Authors: Jason Et al.
Nat Commun 2020;11:4989
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Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways.
Authors: Feng Et al.
Stem Cell Res Ther 2020;11:284
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In vitro Differentiation of Human iPSC-derived Cardiovascular Progenitor Cells (iPSC-CVPCs).
Authors: Kelly A Et al.
Bio Protoc 2020;10:e3755
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A method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96-well microplates.
Authors: Gareth Et al.
Sci Rep 2020;10:18498
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Differentiation of Cardiomyocytes from Human Pluripotent Stem Cells in Fully Chemically Defined Conditions.
Authors: Jizhong Et al.
STAR Protoc 2020;1
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Protocol for the Generation of Human Pluripotent Reporter Cell Lines Using CRISPR/Cas9.
Authors: Ting Et al.
STAR Protoc 2020;1
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Canonical Wnt5b Signaling Directs Outlying Nkx2.5+ Mesoderm into Pacemaker Cardiomyocytes.
Authors: Peidong Et al.
Dev Cell 2019;50:729-743.e5
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Population and Single-Cell Analysis of Human Cardiogenesis Reveals Unique LGR5 Ventricular Progenitors in Embryonic Outflow Tract.
Authors: Kenneth R Et al.
Dev Cell 2019;48:475-490.e7
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Long-term functional maintenance of primary human hepatocytes in vitro.
Authors: Xiang Et al.
Science 2019;364:399
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In Vivo Generation of Post-infarct Human Cardiac Muscle by Laminin-Promoted Cardiovascular Progenitors.
Authors: Yap Et al.
Cell Rep 2019;26:3231
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User-Friendly and Parallelized Generation of Human Induced Pluripotent Stem Cell-Derived Microtissues in a Centrifugal Heart-on-a-Chip.
Authors: Schneider Et al.
Tissue Eng Part A 2019;25:786
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Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Authors: Wang Et al.
Mol Metab 2019;24:80
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TBX18 transcription factor overexpression in human-induced pluripotent stem cells increases their differentiation into pacemaker-like cells.
Authors: Nasser Et al.
J Cell Physiol 2019;234:1534-1546
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End-to-End Platform for Human Pluripotent Stem Cell Manufacturing.
Authors: Puspa R Et al.
Int J Mol Sci 2019;21
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Establishment of A Protocol for In Vitro Culture of Cardiogenic Mesodermal Cells Derived from Human Embryonic Stem Cells.
Authors: Vahdat Et al.
Cell J 2019;20:496
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TMEM88 Inhibits Wnt Signaling by Promoting Wnt Signalosome Localization to Multivesicular Bodies.
Authors: Lee and Evans
iScience 2019;19:267
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Capacitation of human na�ve pluripotent stem cells for multi-lineage differentiation.
Authors: Rostovskaya Et al.
Development 2019;146
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Coculture with noncardiac cells promoted maturation of human stem cell-derived cardiomyocyte microtissues.
Authors: Elena Et al.
J Cell Biochem 2019;120:16681-16691
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Geometrical Patterning and Constituent Cell Heterogeneity Facilitate Electrical Conduction Disturbances in a Human Induced Pluripotent Stem Cell-Based Platform: An In vitro Disease Model of Atrial Arrhythmias.
Authors: Nakanishi Et al.
Front Physiol 2019;10:818
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Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling.
Authors: Kling Et al.
Front Immunol 2018;9:483
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Effects of lung and airway epithelial maturation cocktail on the structure of lung bud organoids.
Authors: Magro-Lopez Et al.
Stem Cell Res.Ther. 2018;9:186
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ETV1 activates a rapid conduction transcriptional program in rodent and human cardiomyocytes.
Authors: Shekhar Et al.
Sci Rep 2018;8:9944
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Efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate iPSCs.
Authors: Lin Et al.
Sci Rep 2018;8:5907
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3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling.
Authors: Ying Et al.
Cell Stem Cell 2018;23:516-529.e5
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Efficient transdifferentiation of human dermal fibroblasts into skeletal muscle.
Authors: George A Et al.
J Tissue Eng Regen Med 2018;12:e918-e936
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Culture in Glucose-Depleted Medium Supplemented with Fatty Acid and 3,3',5-Triiodo-l-Thyronine Facilitates Purification and Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes.
Authors: Lin Et al.
Front Endocrinol (Lausanne) 2017;8:253
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A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells.
Authors: Walko Et al.
Nat Commun 2017;8:14744
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Use of Human Pluripotent Stem Cell Derived-Cardiomyocytes to Study Drug-Induced Cardiotoxicity.
Authors: Liam R Et al.
Curr Protoc Toxicol 2017;73:22.5.1-22.5.22
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Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes.
Authors: Wen Et al.
Stem Cells Transl Med 2017;6:527-538
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Human Pluripotent Stem Cell-Derived Atrial and Ventricular Cardiomyocytes Develop from Distinct Mesoderm Populations.
Authors: Lee Et al.
Cell Stem Cell 2017;21:179
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Degree of tissue differentiation dictates susceptibility to BRAF-driven colorectal cancer.
Authors: Tong
Cell Rep 2017;21(13):3833
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Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development.
Authors: Shi Et al.
Cell Stem Cell 2017;20:675
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WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice.
Authors: Heinrich Et al.
Blood Adv 2017;1:1274-1286
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Label-free imaging of metabolism and oxidative stress in human induced pluripotent stem cell-derived cardiomyocytes.
Authors: Datta Et al.
Biomed Opt Express 2016;7:1690
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Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability.
Authors: Perales-Clemente Et al.
EMBO J 2016;35:1979
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Regulation of WNT Signaling by VSX2 During Optic Vesicle Patterning in Human Induced Pluripotent Stem Cells.
Authors: Capowski Et al.
Stem Cells 2016;34:2625
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Wnt/β-catenin signaling promotes self-renewal and inhibits the primed state transition in na�ve human embryonic stem cells.
Authors: Xu Et al.
Proc Natl Acad Sci U S A 2016;113:E6382
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Sp5 and Sp8 recruit β-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription.
Authors: Kennedy Et al.
Proc Natl Acad Sci U S A 2016;113:3545
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HP Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes.
Authors: Lin Et al.
Stem Cells Transl Med 2016;
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Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids.
Authors: Freedman Et al.
Nat Cell Biol 2015;6:8715
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Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs.
Authors: Lee Et al.
Sci Rep 2015;5:11817
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A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation.
Authors: Lee Et al.
Nat Commun 2015;5:10305
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A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells.
Authors: Richard P Et al.
Stem Cells Transl Med 2015;4:1482-94
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Generation of an expandable intermediate mesoderm restricted progenitor cell line from human pluripotent stem cells.
Authors: Kumar Et al.
Elife 2015;4
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Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales.
Authors: Huebsch Et al.
Tissue Eng Part C Methods 2015;21:467
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Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages.
Authors: Ditadi Et al.
Stem Cell Res 2015;17:580
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Supervised Machine Learning for Classification of the Electrophysiological Effects of Chronotropic Drugs on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Authors: Heylman Et al.
PLoS One 2015;10:e0144572
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Act.-A and Bmp4 levels modulate cell type specification during CHIR-induced cardiomyogenesis.
Authors: Kim Et al.
PLoS One 2015;10:e0118670
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The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells.
Authors: Huang Et al.
Sci Rep 2015;10:413
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Cardiac differentiation of human pluripotent stem cells in scalable suspension culture.
Authors: Ulrich Et al.
Nat Protoc 2015;10:1345-61
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Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.
Authors: Faisy Et al.
PLoS One 2014;9:e111350
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Controlling expansion and cardiomyogenic differentiation of human pluripotent stem cells in scalable suspension culture.
Authors: Kempf Et al.
Stem Cell Reports 2014;3:1132
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Efficient generation of lung and airway epithelial cells from human pluripotent stem cells.
Authors: Huang Et al.
Nat Biotechnol 2014;32:84
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SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development.
Authors: Skelton Et al.
Nat Genet 2014;13:172
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Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium.
Authors: Hojo Et al.
J Biol Chem 2013;288:9924
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I used it as a Wnt pathway inhibitor in Hepatocellular Carcinoma Cells. I used the concentration 5uM and it works really well.