Cell-intrinsic and -extrinsic signaling mechanisms in hematopoiesis are well conserved between zebrafish and mammals, with the exception of a few hematopoietic niche components ( Liao et al., 1998 Murayama et al., 2006 Bertrand and Traver, 2009 Paik and Zon, 2010 Goessling and North, 2011 Zhang and Liu, 2011 Zhang et al., 2013 Frame et al., 2017 Nik et al., 2017 Gore et al., 2018). Many attractive features underpin the success of zebrafish as a model for vertebrate hematopoiesis. Over the past three decades, zebrafish has been established as an important model to study various biological processes during development and homeostasis, including hematopoiesis. In this perspective, we discuss how the zebrafish model has proven beneficial for studying physiological and pathological hematopoiesis and how these novel technologies are transforming the field. Recent technological advances in single-cell transcriptome analysis, epigenetic regulation, proteomics, metabolomics, and processing of large data sets promise to transform the current understanding of normal, abnormal, and malignant hematopoiesis. Finally, zebrafish has been used to model hematopoietic diseases. Moreover, zebrafish enables in vivo imaging of hematopoietic stem cell generation and differentiation during embryogenesis, and adulthood. Several new hematopoietic regulators were identified in genetic and chemical screens using the zebrafish model. Zebrafish is a widely used and well-established model for studying the hematopoietic system. Disruptions in this process have immediate consequences for oxygen transport, responses against pathogens, maintenance of hemostasis and vascular integrity. In vertebrate organisms, billions of differentiated hematopoietic cells need to be continuously produced to replenish the blood cell pool. Hematopoiesis is an optimal system for studying stem cell maintenance and lineage differentiation under physiological and pathological conditions. 2Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.1Department of Hematology, Erasmus MC, Rotterdam, Netherlands.

Posterior blood island zebrafish