Spi-B can functionally replace PU.1 in myeloid but not lymphoid development. EMBO J 2002 May 01;21(9):2220-30
Date
05/01/2002Pubmed ID
11980719Pubmed Central ID
PMC125373DOI
10.1093/emboj/21.9.2220Scopus ID
2-s2.0-0036566050 (requires institutional sign-in at Scopus site) 39 CitationsAbstract
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.
Author List
Dahl R, Ramirez-Bergeron DL, Rao S, Simon MCAuthor
Sridhar Rao MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Lineage
Cells, Cultured
DNA-Binding Proteins
Gene Targeting
Lymphocytes
Macrophages
Mice
Myeloid Cells
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-ets
Stem Cells
Trans-Activators
Transcription Factors
