- Pluripotent Stem Cells Research
- Cardiac electrophysiology and arrhythmias
- Tissue Engineering and Regenerative Medicine
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Electrospun Nanofibers in Biomedical Applications
- CRISPR and Genetic Engineering
- Neuroscience and Neuropharmacology Research
- Caveolin-1 and cellular processes
- Cardiac Fibrosis and Remodeling
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Mesenchymal stem cell research
- Biomedical Ethics and Regulation
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Ion Transport and Channel Regulation
- Genetic Neurodegenerative Diseases
- Cardiovascular Function and Risk Factors
- RNA and protein synthesis mechanisms
- Gut microbiota and health
- RNA Interference and Gene Delivery
University of Wisconsin–Madison
2016-2025
University of Wisconsin System
2015-2021
Cellular Research (United States)
2021
Beijing Anzhen Hospital
2021
National Clinical Research
2021
Capital Medical University
2021
University at Albany, State University of New York
2021
Highland Community College - Illinois
2005-2021
Digital Proteomics (United States)
2015
WiCell
2005-2014
Human pluripotent stem cells (hPSCs) offer the potential to generate large numbers of functional cardiomyocytes from clonal and patient-specific cell sources. Here we show that temporal modulation Wnt signaling is both essential sufficient for efficient cardiac induction in hPSCs under defined, growth factor-free conditions. shRNA knockdown β-catenin during initial stage hPSC differentiation fully blocked cardiomyocyte specification, whereas glycogen synthase kinase 3 inhibition at this...
Human induced pluripotent stem (iPS) cells hold great promise for cardiovascular research and therapeutic applications, but the ability of human iPS to differentiate into functional cardiomyocytes has not yet been demonstrated. The aim this study was characterize cardiac differentiation potential generated using OCT4, SOX2, NANOG, LIN28 transgenes compared embryonic (ES) cells. ES were differentiated embryoid body (EB) method. time course developing contracting EBs comparable cell lines,...
Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid bodies (EBs) composed of derivatives all three germ layers. Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs); however, the types human CMs and their functional properties are unknown. This study characterizes contractions action potentials (APs) beating EB cultured for 40 to 95 days. Spontaneous electrical field-stimulated were measured with video edge-detection microscopy....
Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes; however, the electrophysiological properties of hiPSC-derived cardiomyocytes have yet to be fully characterized. We performed detailed characterization highly pure cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating using a perforated patch method and had atrial-, nodal-, ventricular-like properties. Ventricular-like APs more common maximum diastolic close those human...
Background— Congenital long-QT syndrome (LQTS) is a primary arrhythmogenic stemming from perturbed cardiac repolarization. LQTS, which affects ≈1 in 3000 persons, 1 of the most common causes autopsy-negative sudden death young. Since sentinel discovery channel gene mutations LQTS 1995, hundreds 8 susceptibility genes have been identified. All genotypes represent defects (ie, ion channelopathy) except LQT4, functional channelopathy because ankyrin-B. Approximately 25% remains unexplained...
Cardiomyocytes (CMs) differentiated from human pluripotent stem cells (PSCs) are increasingly being used for cardiovascular research, including disease modeling, and hold promise clinical applications. Current cardiac differentiation protocols exhibit variable success across different PSC lines primarily based on the application of growth factors. However, extracellular matrix is also fundamentally involved in development earliest morphogenetic events, such as gastrulation.We sought to...
L-type Ca(2+) channels play a critical role in regulating Ca(2+)-dependent signaling cardiac myocytes, including excitation-contraction coupling; however, the subcellular localization of and their regulation are incompletely understood. Caveolae specialized microdomains plasmalemma rich molecules supported by structural protein caveolin-3 muscle. Here we demonstrate that subpopulation is localized to caveolae ventricular myocytes as part macromolecular complex necessary for...
The impact of gut microbiota on the regulation host physiology has recently garnered considerable attention, particularly in key areas such as immune system and metabolism. These are also crucial for pathophysiology repair after myocardial infarction (MI). However, role context MI remains to be fully elucidated. To investigate effects cardiac MI, C57BL/6J mice were treated with antibiotics 7 days before deplete mouse microbiota. Flow cytometry was applied examine changes cell composition...
There is no consensus in the stem cell field as to what constitutes mature cardiac myocyte. Thus, helping formalize a molecular signature for myocyte maturation would advance field. In mammalian heart, inactivation of "fetal" TNNI gene, TNNI1 (ssTnI), together temporal concert with its stoichiometric replacement by adult gene product, TNNI3 (cTnI), represents quantifiable ratiometric signature. We examined isoform transition human induced pluripotent (iPSC) myocytes (hiPSC-CMs) and found...
Abstract Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. The limited availability of human CFs from native impedes investigations CF biology their role Human pluripotent stem cells (hPSCs) provide a highly renewable genetically defined cell source, but efficient methods to generate hPSCs have not been described. Here, we show differentiation using sequential modulation Wnt FGF signaling second field progenitors that efficiently give rise...
Abstract Aims Caveolin-3 is essential for the formation of caveolae in cardiomyocytes. Caveolar microdomains have been shown to regulate distribution signalling proteins such as beta-adrenoceptors (βAR) and may act membrane reserves protect cell from damage during mechanical stretch. Myocardial stretch occurs haemodynamic overload be normal (e.g. exercise) or pathological heart failure); therefore, it important understand effect on pathways associated with mechanosensitive structures,...
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a powerful in vitro tool to investigate disease mechanisms and perform patient-specific drug screening. To date, electrophysiological analysis of iPSC-CMs has been limited single-cell recordings or low-resolution microelectrode array mapping small cardiomyocyte aggregates. New methods generating optically impulse propagation large human iPSC-CM cardiac monolayers are needed.Our first aim was develop an imaging...
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are being increasingly used to model heart diseases. hiPSC-CMs generated by earlier aggregation-based methods (i.e., embryoid body) often lack functional sarcoplasmic reticulum (SR) Ca stores characteristic of mature mammalian CMs. Newer monolayer-based cardiac differentiation Matrigel sandwich or small molecule-based differentiation) produce high purity and yield, but their handling has not been comprehensively...