Initially

described in 1876 by von Kupffer as liver Sternzellen (“star-shaped cells”) and then by Ito as vitamin-A storing cells, HSCs have since been well characterized, and much is known about their molecular and cellular biology.1 However, the exact developmental origin of HSCs remains unknown, and until recently we have lacked the capabilities to observe stellate cell activation in vivo. Moreover, we have been unable to discover novel chemical and genetic factors that regulate stellate cell development and activation. In the current issue of HEPATOLOGY, Yin et al.2 describe a novel cell population in the zebrafish liver that exhibits all the hallmarks of HSCs in mammals, from their morphology, to their capacity to store fat and vitamin A, to their expression profile and activation in response to injury. How can this newly discovered cell type in the selleck chemical zebrafish help us understand HSC regulation and improve patient outcomes? HSC, hepatic stellate cell. Over the past two decades,

zebrafish have been established as an excellent model to study early development and organogenesis. The embryos are transparent, allowing for direct visualization of in vivo processes, and they develop rapidly, so that they harbor differentiated hepatocytes by 3 days of life.3, 4 Zebrafish are equally amenable to forward genetic and chemical genetic screening approaches. Despite several hundreds of millions of years of divergent evolution, the zebrafish gastrointestinal tract and PLX4032 nmr liver are remarkably similar to those MCE of mammals, both in their cellular organization and in the molecular signals governing organ development, growth, regeneration, and malignant transformation.5, 6 Using transgenic zebrafish lines, as well as by in situ hybridization and immunocytological methods, hepatocytes, biliary epithelial cells and endothelial cells can be identified with specific markers.3, 7 Yin et al. describe the discovery

of HSCs as a novel cell type in the zebrafish liver. Their study made use of recently generated transgenic reporter fish, which highlight the expression of the bHLH transcription factor hand2 (heart and neural crest derivates expressed transcript 2). This gene, expressed early in the lateral plate mesoderm, had been described previously by the authors as an essential factor for gut looping and laterality during early endoderm development.8 The authors demonstrate the morphological similarity to mammalian HSCs, with a star-shaped appearance and cellular processes that lie in close proximity to endothelial cells, expressing desmin and glial fibrillary acidic protein. The authors further elucidate the developmental origin of this cell type in the mesoderm, which had been shown via lineage-tracing experiments to be the source of HSCs in mouse liver.9 More importantly, Yin et al.