Stem Cell Model of Hematopoiesis

Hematopoietic stem cells (HSC) are characterized by their capacity of self-renewal, multi-lineage differentiation, and the ability to rescue lethally irradiated hosts. Both murine and human studies have attempted to characterize and purify HSC based on surface phenotypes, metabolic markers, in-vitro clonogenic and in-vivo competitive repopulation assays. The cell-fate of HSC is under intrinsic regulation by various transcription factors, including Hox and SCL genes, cyclin-dependent kinase inhibitors and telomerase, and extrinsic regulation by various signaling pathways involved in embryonic development, including the Notch, Wnt and bone morphogenetic proteins (BMP) pathways. Recent advances in genome research and gene profiling technologies have begun to unravel the regulatory mechanism of HSC by novel genes with hitherto unknown functions in hematopoiesis. The stem cell model of hematopoiesis has also shed light on the concepts of leukemic stem cells (LSC), which involves the presence of a rare population of cells that share the essential HSC attributes of self-renewing, replication and differentiation into progenies of leukemic blasts. Keywords: cDNA microarray, MAPK, epidermal growth factor (EGF), stroma, CBF-1