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Directing stem cell fate requires knowledge of how signaling networks integrate temporally and spatially segregated stimuli. We developed and validated a computational model of signal transducer and activator of transcription-3 (Stat3) pathway kinetics, a signaling network involved in embryonic stem cell (ESC) self-renewal. Our analysis identified novel(More)
Highly ordered aggregates of cells, or niches, regulate stem cell fate. Specific tissue location need not be an obligatory requirement for a stem cell niche, particularly during embryogenesis, where cells exist in a dynamic environment. We investigated autoregulatory fixed-location-independent processes controlling cell fate by analyzing the spatial(More)
Stem cells convert graded stimuli into all-or-nothing cell-fate responses. We investigated how embryonic stem cells (ESCs) convert leukemia inhibitory factor (LIF) concentration into an all-or-nothing cell-fate decision (self-renewal). Using a combined experimental/computational approach we demonstrate unexpected switch-like (on/off) signaling in response(More)
Stem cell fate is governed by the integration of intrinsic and extrinsic positive and negative signals upon inherent transcriptional networks. To identify novel embryonic stem cell (ESC) regulators and assemble transcriptional networks controlling ESC fate, we performed temporal expression microarray analyses of ESCs after the initiation of commitment and(More)
SUMMARY Combining high-content screening (HCS) with random gene-trap mutagenesis could be a powerful tool to investigate transcriptional networks, cell signaling, chemical genetics, and developmental processes. However, a critical limitation has been poor quantification of reporter expression per cell. To overcome this hurdle, we generated a variety of(More)
The mode of ligand presentation has a fundamental role in organizing cell fate throughout development. We report a rapid and simple approach for immobilizing signaling ligands to maleic anhydride copolymer thin-film coatings, enabling stable signaling ligand presentation at interfaces at defined concentrations. We demonstrate the utility of this platform(More)
Stem cells and their derivatives represent a renewable source of cells for therapeutic applications. However, the inability to quantitatively integrate and exploit the effects of multiple parameters on the fate of stem cells limits their use in clinical applications. To address this, we developed a computational model that combines probabilistic,(More)
PURPOSE OF REVIEW Strategies to manipulate stem cells for therapeutic applications are limited by our inability to control or predict stem cell fate decisions in response to exogenous stimuli. This review focuses on the mechanisms by which exogenous stimuli influence cell fate. RECENT FINDINGS Limitations in our ability to control cell fate arises from(More)
Hemodynamic monitoring has long formed the cornerstone of heart failure (HF) and pulmonary hypertension diagnosis and management. We review the long history of invasive hemodynamic monitors initially using pulmonary artery (PA) pressure catheters in the hospital setting, to evaluating the utility of a number of implantable devices that can allow for(More)