HEMATOPOIETIC STEM-CELLS AND LYMPHOID PROGENITORS EXPRESS DIFFERENT IKAROS ISOFORMS, AND IKAROS IS LOCALIZED TO HETEROCHROMATIN IN IMMATURELYMPHOCYTES

The generation of lymphoid cells in mice depends on the function of th e Ikaros protein, Ikaros has been characterized as a lymphoid-restrict ed, zinc-finger transcription factor that is derived from an alternati vely spliced message, Ikaros knockout mice have defects in multiple ce ll lineages, raising the question of whether the protein regulates mul tiple committed progenitors and/or multipotent stem cells. To address this issue, we examined Ikaros expression in purified populations of m ultipotent cells and more committed progenitors, We found that the DNA -binding isoforms of Ikaros were localized in the nucleus of the most primitive hematopoietic stem cell subset. Changes in the RNA splicing pattern of Ikaros occurred at two stages: (i) as long-term self-renewi ng stem cells differentiated into short-term self-renewing stem cells and (ii) as non-self-renewing multipotent progenitors differentiated i nto lymphoid-committed progenitors, Unexpectedly, we found Ikaros loca lized to heterochromatin in Abelson-transformed pre-B lymphocytes by u sing immunogold electron microscopy, These observations suggest a comp lex role for Ikaros in lymphoid development.