Spi-B can functionally replace PU.1 in myeloid but not lymphoid development

Richard Dahl, Diana L. Ramirez-Bergeron, Sridhar Rao, M. Celeste Simon

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Mature macrophages, neutrophils and lymphoid cells do not develop in PU.1-1- 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.1Spi-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-2-1- 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.

Original languageEnglish (US)
Pages (from-to)2220-2230
Number of pages11
JournalEMBO Journal
Volume21
Issue number9
DOIs
StatePublished - May 1 2002
Externally publishedYes

Keywords

  • Hematopoiesis
  • PU.1
  • Spi-B

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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