Systems level investigation of liver transcriptome in physiology and pathology

Abstract

Metabolism is an integral part of cellular physiology, with the liver as the central organ for a wide range of metabolic functions and homeostasis. The liver, unlike other organs, has a remarkable capacity to regenerate after partial loss of its mass, thus maintaining a constant liver-to-body weight ratio to preserve homeostasis. In an injury-free liver, the turnover of regeneration is very slow, but in the presence of an injury or perturbation, the regenerative response is triggered as a reparative strategy. Perturbations interfering with liver functions and disturbing the homeostatic state have serious repercussions leading to metabolic disorders like hepatic steatosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Ageing is one risk factor that increases the susceptibility to these diseases. The regenerative ability of the liver has been used to treat these diseases in the form of liver transplantation and partial liver resection, but recurrence of the disease is often observed after a few years. Understanding the molecular network that controls liver function and its regenerative ability in health and disease is crucial for developing clinical applications. The emergence of high throughput omics technologies provides a scope to develop a systems-level understanding of the disease. In this direction, we attempt to understand the pathophysiology of the liver by adopting systems biology approach for omics data interpretation. newlineTissue homeostasis and regeneration depend on the reversible transitions between quiescence (G0) and cell proliferation. During regeneration, the liver needs to maintain the essential metabolic tasks along with the fulfilment of metabolic requirements for hepatocyte growth and division. To understand the regulatory mechanisms involved in balancing the liver function and proliferation demand after injury or resection, we analyzed RNA sequencing temporal data of liver regeneration after two-thirds partial hepatectomy (PH) u