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

EMBO J. 2002 May 1;21(9):2220-30. doi: 10.1093/emboj/21.9.2220.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Cell Lineage / physiology*
  • Cells, Cultured
  • DNA-Binding Proteins / physiology*
  • Gene Targeting
  • Lymphocytes / physiology*
  • Macrophages / physiology
  • Mice
  • Myeloid Cells / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-ets
  • Stem Cells / physiology
  • Trans-Activators / physiology*
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Trans-Activators
  • Transcription Factors
  • proto-oncogene protein Spi-1
  • SPIB protein, human