Molecular switches and developmental potential of adult stem cells.

Abstract

Stem cell commitment and differentiation entails the successive loss of self-renewal and developmental potential, and results in the final restriction to a terminally differentiated mature cell type. Hematopoiesis, the development of blood cells from hematopoietic stem cells in bone marrow, is particularly well studied, and at different branching points within the hematopoietic system multiple developmental intermediates have been identified. Here we describe a Flt3+ CD11b+ multipotent progenitor that can be amplified in vitro by a specific cytokine combination to high cell numbers, and following adoptive transfer into syngeneic mice, it generates dendritic cells but also additional mature cell types. By employing gene expression profiling with DNA microarrays and knockout mouse models, we demonstrate that the helix-loop-helix (HLH) transcription factor Id2 (inhibitor of DNA binding/differentiation 2) acts as a molecular switch in development of Langerhans cells (LCs), the cutaneous contingent of dendritic cells (DCs), and of specific DC subsets and B cells.