Development of Hematopoietic Stem Cells in Zebrafish

Abstract

Hematopoietic stem cells (HSCs) are a rare population of cells with the remarkable abilities to both self-renew and differentiate into all types of mature blood cells. Understanding of the developmental mechanisms of HSCs is of great importance to instruct and expand HSCs from pluripotent precursors, such as induced pluripotent stem cells (iPSCs). The zebrafish is a unique vertebrate model in which numerous elegant experimental approaches can be applied to the study of HSC development, including live-imaging, chemical and genetic screening, and genome editing. HSCs are specified from a shared vascular precursor, the angioblast, and arise directly from the ventral floor of the dorsal aorta. HSCs then migrate to a transient hematopoietic organ, the caudal hematopoietic tissue, where microenvironmental niche cells promote the expansion of HSCs prior to the colonization of the kidney, the final adult hematopoietic organ in zebrafish. Over the past decade, a number of intrinsic and extrinsic signaling molecules involved in the specification, maintenance, migration, and proliferation of HSCs have been identified in the zebrafish embryo. Importantly, despite evolutional divergence, the genetic programs governing HSC development are highly conserved among vertebrates, indicating that studies in zebrafish may be translated to regenerative medicine using human iPSCs. This chapter highlights the current knowledge and recent advances regarding the cellular origin and molecular regulation of HSC development in zebrafish.