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  Hematopoiesis
  Back to Immunology Main

Recent developments in stem cell biology have generated much excitement about the potential for cell-based therapies in a variety of clinical applications, such as treating Parkinson’s disease, leukemia, and spinal cord injuries (Orkin, 2000). Crucial to the success of these therapies is the detailed understanding of how the cells remain stem cells, and the cues that they require to commit themselves to specific cell fates.

In hematopoiesis, mature differentiated cells are continuously replaced by stem cells. These stem cells reside in the bone marrow, and have the ability to self-renew as well as to differentiate into a wide variety of blood cell types, a process that is very tightly regulated. During differentiation, cells become committed to a lineage fate, and lose the ability to differentiate into an alternate cell lineage. There are catastrophic consequences to aberrant hematopoiesis, such as leukemia, lymphoma, etc. A variety of studies using GeneChip® arrays have focused on the normal cell development or on the cell-lineage switch (Schweitzer, 2004; Araki, 2004). Understanding the nature of stem cells, as well as the molecular process by which these cells acquire their specific cell fate is crucial to the success of cell-based therapies.

Initial microarray profiling studies focused on pure hematopoietic stem cells (HSC) and their comparison to neural and embryonic stem cells (Ivanova, 2003; Ramalho-Santos, 2002). A dynamic analysis of HSC undergoing self-renewal and differentiation into a variety of cell lineages has also been accomplished using GeneChip® Murine U74Av2 Arrays (Bruno, 2004). This study found that HSC are characterized by a complex transcriptional profile in which the cells are genetically primed to switch to multiple cell fate pathways. Additionally, some genes were identified that may be important for self-renewal. Early differentiation was characterized by a general decrease in gene expression, and genetic candidates were found early in the cell fate decision pathway that may be early precursors of unilineage commitment.
Related Scientific Publications

Orkin, S.H., and Morrison, S.J. Stem-cell competition. Nature 418, 25-7 (2000).

Schweitzer, B. L. and DeKoter, R. P. Analysis of gene expression and Ig transcription in PU.1/Spi-B-deficient progenitor B cell lines. Journal of Immunology. 172, 144-54 ( 2004 ).

Araki, H., et al. Reprogramming of human postmitotic neutrophils into macrophages by growth factors . Blood.  103, 2973-80 ( 2004 ).

Ivanova, N. B. et al. Response to comments on " 'stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science.  298, 601-4 ( 2003).

Ramalho-Santos, M. et al. "Stemness": transcriptional profiling of embryonic and adult stem cells.
Science. 298, 597-600 ( 2002).

Bruno, L., et al. Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. Molecular and Cellular Biology.  24, 741-56 ( 2004 ).

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