Acute avian leukemia viruses as tools to study hematopoietic cell differentiation.

Abstract

Hematopoiesis is a multistep process during which an uncommitted, self-renewing progenitor divides and differentiates along one of eight distinct lineages, each with a unique function and each expressing a unique complement of proteins enabling them to carry out these functions. In adult vertebrates, multipotent hematopoietic precursors reside within the microenvironment of the bone marrow where they undergo a progressive maturation and commitment to one of several lymphoid and nonlymphoid cell lineages. Regulation of normal hematopoietic development requires an intricate set of cues from stromal cells involving signaling via soluble growth factors, cell-cell and cell-extracellular matrix interactions (Quesenberry 1992). Analysis of the cellular intermediates in these differentiation pathways has been greatly facilitated by the development of in vitro colony forming assays for multipotent and monopotent hematopoietic precursors and the identification of cytokines which regulate their growth and differentiation (Metcale 1984, 1988). Nevertheless, analysis of the molecular mechanisms governing differentiation and commitment to a given lineage has been technically difficult as bone marrow precursors are present in relatively low frequency and reagents allowing their isolation have only recently been developed. In addition, obtaining clonal precursor cells in sufficient numbers for biochemical analysis has been problematic since these precursors have a limited life span in vitro.