A Functional Genomics Approach to Hematopoietic Stem Cell Regulation

Elucidation of the molecular mechanisms that are responsible for regulating the most basic properties of stem cells, self-renewal, and differentiation remains a major challenge in hematopoietic stem cell biology. We have taken a functional genomics approach towards revealing these mechanisms. Previous studies of the fetal liver genetic program led to the development of Stem Cell Database (SCDb, http://stemcell.princeton.edu ), a resource for the stem cell community. These studies have been expanded to include the microenvironmental component of hematopoiesis and are the focus herein. In our efforts to study the microenvironmental component we have identified a stromal cell line, AFT024, which serves as a surrogate stem cell niche. The line provides a milieu that facilitates the maintenance of transplantable mouse and human stem cells as well as the generation of large populations of committed progenitors. In a manner mirroring the work done with the SCDb, we provide an online resource, Stromal Cell Database, StroCDB (http://stromalcell.princeton.edu ), that is a compendium of information and data derived from biological and molecular studies of this surrogate niche. These include bioinformatic analyses of over 6000 clones derived from a subtracted library enriched for messages expressed in AFT024 as well as data derived from custom expression arrays developed from this library. Herein we describe these efforts and provide a guide for navigating the database and mining the information contained within.