A Reporter Mouse Reveals Lineage-Specific and Heterogeneous Expression of IRF8 during Lymphoid and Myeloid Cell Differentiation.

Wang, H; Yan, M; Sun, J; Jain, S; Yoshimi, R; Abolfath, SM; Ozato, K; Coleman, WG; Ng, AP; Metcalf, D; DiRago, L; Nutt, SL; Morse, HC

Author(s): Wang, H; Yan, M; Sun, J; Jain, S; Yoshimi, R; Abolfath, SM; Ozato, K; Coleman, WG; Ng, AP; Metcalf, D; DiRago, L; Nutt, SL; Morse, HC;
Details: Publication Year 2014-07-14,Volume 193,Issue #4,Page 1766-1777
Journal Title: Journal of Immunology
Publication Type: JOURNAL ARTICLE
Abstract: The IFN regulatory factor family member 8 (IRF8) regulates differentiation of lymphoid and myeloid lineage cells by promoting or suppressing lineage-specific genes. How IRF8 promotes hematopoietic progenitors to commit to one lineage while preventing the development of alternative lineages is not known. In this study, we report an IRF8-EGFP fusion protein reporter mouse that revealed previously unrecognized patterns of IRF8 expression. Differentiation of hematopoietic stem cells into oligopotent progenitors is associated with progressive increases in IRF8-EGFP expression. However, significant induction of IRF8-EGFP is found in granulocyte-myeloid progenitors and the common lymphoid progenitors but not the megakaryocytic-erythroid progenitors. Surprisingly, IRF8-EGFP identifies three subsets of the seemingly homogeneous granulocyte-myeloid progenitors with an intermediate level of expression of EGFP defining bipotent progenitors that differentiation into either EGFP(hi) monocytic progenitors or EGFP(lo) granulocytic progenitors. Also surprisingly, IRF8-EGFP revealed a highly heterogeneous pre-pro-B population with a fluorescence intensity ranging from background to 4 orders above background. Interestingly, IRF8-EGFP readily distinguishes true B cell committed (EGFP(int)) from those that are noncommitted. Moreover, dendritic cell progenitors expressed extremely high levels of IRF8-EGFP. Taken together, the IRF8-EGFP reporter revealed previously unrecognized subsets with distinct developmental potentials in phenotypically well-defined oligopotent progenitors, providing new insights into the dynamic heterogeneity of developing hematopoietic progenitors.
Publisher: AMER ASSOC IMMUNOLOGISTS
Research Division(s): Cancer And Haematology; Molecular Immunology
Publisher's Version: https://doi.org/10.4049/jimmunol.1301939
NHMRC Grants: NHMRC/1016647,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2014-07-30 02:50:01