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Spi‐B can functionally replace PU.1 in myeloid but not lymphoid development
Author(s) -
Dahl Richard,
RamirezBergeron Diana L.,
Rao Sridhar,
Simon M.Celeste
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.9.2220
Subject(s) - biology , myeloid , haematopoiesis , microbiology and biotechnology , b cell , lymphopoiesis , embryonic stem cell , progenitor cell , phenotype , stem cell , embryoid body , immunology , genetics , antibody , adult stem cell , gene
Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1 −/− mice. In contrast, mice lacking the highly related protein Spi‐B generate all hematopoietic lineages but display a B‐cell receptor signaling defect. These distinct phenotypes could result from functional differences between PU.1 and Spi‐B or their unique temporal and tissue‐specific expression (PU.1: myeloid and B cells; Spi‐B: B cells only). To address this question, we introduced the Spi‐B cDNA into the murine PU.1 locus by homologous recombination. In the absence of PU.1, Spi‐B rescued macrophage and granulocyte development when assayed by in vitro differentiation of embryonic stem cells. Adherent, CD11b + /F4/80 + cells capable of phagocytosis were detected in PU.1 Spi‐B/Spi‐B embryoid bodies, and myeloid colonies were present in hematopoietic progenitor assays. Despite its ability to rescue myeloid differentiation, Spi‐B did not rescue lymphoid development in a RAG‐2 −/− complementation assay. These results demonstrate an important difference between PU.1 and Spi‐B. Careful comparison of these Ets factors will delineate important functional domains of PU.1 involved in lymphocyte lineage commitment and/or maturation.