From Seeing to Simulating: A Survey of Imaging Techniques and Spatially-Resolved Data for Developing Multiscale Computational Models of Liver Regeneration.

Liver regeneration, which leads to the re-establishment of organ mass, follows a specifically organized set of biological processes acting on various time and length scales. Computational models of liver regeneration largely focused on incorporating molecular and signaling detail have been developed by multiple research groups in the recent years. These modeling efforts have supported a synthesis of disparate experimental results at the molecular scale.

A Spatial Model of Hepatic Calcium Signaling and Glucose Metabolism Under Autonomic Control Reveals Functional Consequences of Varying Liver Innervation Patterns Across Species.

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents.

Causality Analysis and Cell Network Modeling of Spatial Calcium Signaling Patterns in Liver Lobules.

Dynamics as well as localization of Ca transients plays a vital role in liver function under homeostatic conditions, repair, and disease. In response to circulating hormonal stimuli, hepatocytes exhibit intracellular Ca responses that propagate through liver lobules in a wave-like fashion. Although intracellular processes that control cell autonomous Ca spiking behavior have been studied extensively, the intra- and inter-cellular signaling factors that regulate lobular scale spatial patterns and wave-like propagation of Ca remain to be determined.

Single-Cell Gene Expression Analysis Identifies Chronic Alcohol-Mediated Shift in Hepatocyte Molecular States After Partial Hepatectomy.

The analysis of molecular states of individual cells, as defined by their mRNA expression profiles and protein composition, has gained widespread interest in studying biological phenomena ranging from embryonic development to homeostatic tissue function and genesis and evolution of cancers. Although the molecular content of individual cells in a tissue can vary widely, their molecular states tend to be constrained within a transcriptional landscape partly described by the canonical archetypes of a population of cells. In this study, we sought to characterize the effects of an acute (partial hepatectomy) and chronic (alcohol consumption) perturbation on the molecular states of individual hepatocytes during the onset and progression of liver regeneration.

Computational Modeling of Spatiotemporal Ca(2+) Signal Propagation Along Hepatocyte Cords.

Objective: The purpose of this study is to model the dynamics of lobular Ca(2+) wave propagation induced by an extracellular stimulus, and to analyze the effect of spatially systematic variations in cell-intrinsic signaling parameters on sinusoidal Ca(2+) response.

Methods: We developed a computational model of lobular scale Ca(2+) signaling that accounts for receptor- mediated initiation of cell-intrinsic Ca(2+) signal in hepatocytes and its propagation to neighboring hepatocytes through gap junction-mediated molecular exchange.

Results: Analysis of the simulations showed that a pericentral-to-periportal spatial gradient in hormone sensitivity and/or rates of IP3 synthesis underlies the Ca(2+) wave propagation.