MTG16, a target of the t(16;21), regulates hematopoietic stem cell mobilization and progenitor cell proliferation.. Mus musculus

A single normal hematopoietic stem cell (HSC) is sufficient to regenerate the entire blood system after bone marrow transplantation. This process requires not only rapid mobilization of the stem cell into the cell cycle, but also the proliferation of committed progenitor cells to provide functional mature cells until HSC progeny have accumulated to sufficient numbers1. Gene disruption strategies have dissected the regulatory pathways and identified critical factors that mediate the decision of a stem cell to self-renew and quiesce or to enter the rapidly expanding progenitor cell pool to populate the various hematopoietic cell lineages. However, only a very limited number of the transcriptional regulators and chromatin remodeling factors that are recruited by DNA binding factors have been pinpointed as contributors to stem cell functions. Here, we show that the transcriptional co-repressor Myeloid Translocation Gene on chromosome 16 (Mtg16), which is targeted by the t(16;21) in acute myeloid leukemia, is required for long-term hematopoietic stem cell functions and suppression of stem cell mobilization. Although there are no dramatic defects in the allocation of cells to any of the major hematopoietic cell lineages, inactivation of Mtg16 impairs the rapid expansion of stem/progenitor cells, which is required after bone marrow transplantation. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc complements the Mtg16-/- defect. Keywords: Knock-out analysis, genetic modification Overall design: The lineage negative fraction of bone marrow from 4 age and sex match wild type (WT_BM) or Mtg16-null (NULL_BM) mice was pooled for total RNA extraction. The samples were analyzed in two different microarray lots (rep1 and rep2).