A defined number of hematopoietic stem cell (HSC) clones are born during development and expand to form the pool of adult stem cells. An intricate balance between self-renewal and differentiation of these HSCs supports hematopoiesis for life. HSC fate is determined by complex transcription factor networks that drive cell-type specific gene programs.
View Article and Find Full Text PDFThe hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with hematopoietic stem and progenitor cells (HSPCs). The molecular factors that specify niche endothelial cells and orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression and chromatin accessibility analyses in zebrafish, we define a conserved gene expression signature and cis-regulatory landscape that are unique to sinusoidal endothelial cells in the HSPC niche.
View Article and Find Full Text PDFTissue-specific stem cells persist for a lifetime and can differentiate to maintain homeostasis or transform to initiate cancer. Despite their importance, there are no described quality assurance mechanisms for newly formed stem cells. We observed intimate and specific interactions between macrophages and nascent blood stem cells in zebrafish embryos.
View Article and Find Full Text PDFCurr Opin Hematol
January 2021
Purpose Of Review: Myeloid cells contribute to immune response to infection and tissue regeneration after injury as well as to the developmental induction of the hematopoietic system overall. Here we review recent uses of zebrafish to advance the study of myeloid biology in development and disease.
Recent Findings: Recent studies have made use of advanced imaging and genetic strategies and have highlighted key concepts in myeloid cell behavior.
Collecting large numbers of rare cells for high-throughput molecular analysis remains a technical challenge, primarily due to limitations in existing technologies. In developmental biology this has impeded single-cell analysis of primordial organs, which derive from few cells. In this study, we share novel transgenic lines for rapid cell enrichment from zebrafish embryos using human surface antigens for immunological binding and magnetic sorting.
View Article and Find Full Text PDFRecent advances in CRISPR/Cas gene editing technology have significantly expanded the possibilities and accelerated the pace of creating genetically engineered animal models. However, CRISPR/Cas-based strategies designed to precisely edit the genome can often yield unintended outcomes. Here, we report the use of zygotic CRISPR/Cas9 injections to generate a knock-in GFP reporter mouse at the Gdf11 locus.
View Article and Find Full Text PDFEach stem cell resides in a highly specialized anatomic location known as the niche that protects and regulates stem cell function. The importance of the niche in hematopoiesis has long been appreciated in transplantation, but without methods to observe activity in vivo, the components and mechanisms of the hematopoietic niche have remained incompletely understood. Zebrafish have emerged over the past few decades as an answer to this.
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