The hematopoieac stem cell has the ability to self-renew as well us the ability to commit to a number of differentiation pathways. Much is known about the in vivo developmental behavior of the stem cell population through many years of mouse and human transplantation studies. In addition, the physical cellular phenotype of the stern cell has been described through numerous purification strategies. In spite of the large amount of available information, the exact molecular mechanisms which mediate the choice between self-renewal and commitment which occurs during stem cell division remain almost completely obscure. As a comprehensive approach to shed light on this issue we have: 1 ) embarked on a broad wide ranging effort to identify the gene expression patterns which exist in undifferentiated and highly purified mouse and human stem cells, 2) begun to analyze how these gene expression profiles are modified in response to cytokine-induced proliferation and differentiation, 3) developed an in vitro correlate of the hematopoietic microenvironment and have shown that this culture system can effectively support the establishment and long-term maintenance of the entire primitive stem/ progenitor cell hierarchy and 4) analyzed the panel of gene products specifically expressed in a stromal cell line which represents a candidate stem cell microenvironmental niche. To date our efforts have yielded approximately 1,000 cDNA sequences which are candidates for genes specifically expressed in stem/progenitor ceils but not in more mature blood cell lineages. In addition, over 500 sequences have been analyzed from the stromal cell line. Collectively these studies, while far from complete, have already yielded a considerable number of interesting molecules. The predicted amino acid sequences of these molecules strongly suggest important roles in the biology of the hematopoietic stem cell and microenvironment.
|Number of pages||1|
|State||Published - 1997|