In vitro differentiation models of human CD34+ hematopoietic progenitor/stem cells have contributed significantly to our current understanding of dendritic cell (DC) development. DC sublineages seem to arise from common progenitors with monocytic cells. These progenitors seem to respond to instructive signals from cytokine receptors and steroids to follow defined sublineage differentiation pathways. Transcriptional processes involved in the regulation of lineage fate decisions of putative common DC progenitors remain poorly defined, as is our knowledge of the identities of DC precursors in vivo. Most likely, tissue-specific microenvironmental signals, including tumor-derived signals, critically modulate DC phenotype and function in vivo.

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