The Lineage and Clonal Relationships of the Primitive Blood

Western Michigan University, Kalamazoo MI

Investigators

Abstract

The central aim of this project is to understand the lineage relationships between the blood cell types that arise in the early vertebrate embryo. In vertebrates, hematopoietic stem cells produce the adult blood, termed the definitive blood. These stem cells produce complex lineages that develop into a complete array of adult blood histotypes. However, in the early embryo, the first blood - the primitive blood - forms from simple lineages from cells termed hemangioblasts. Illuminating the common elements in the emergence of these blood types will help in understanding the genetically encoded mechanisms that control blood cell development. The major approach of this project is to fluorescently label cells, follow them in a live embryo (the zebrafish) using time lapse microscopy and later to identify the progeny of the labeled cells using gene expression studies. This project will first establish the lineage relationships between the major blood divisions, the primitive and definitive lineages, and between major subdivisions, such as erythroid and myeloid lineages. The project will also establish when and where developmental restrictions occur in the blood lineage. By collecting all the divisions of the clones in a living embryo, this project will set a major milestone in the understanding of hematopoiesis: the construction of the first in vivo blood lineage in any creature. A better understanding of the emergence of cells in the hematopoietic system will ultimately lead to the ability to better understand blood-specific stem cells in general and help in the derivation of hematopoietic stem cells from in vitro-derived embryonic sources. This project will fund the training of both undergraduate and graduate students in developmental biology and genetics; these research findings, including images and time-lapse movies, will be made available over the internet for research and instructional uses.