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

35 Citations (Scopus)

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

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B-Lymphocytes
Macrophages
Cells
Assays
Lymphocytes
Embryoid Bodies
Cytophagocytosis
Homologous Recombination
Myeloid Cells
Embryonic Stem Cells
Stem cells
Granulocytes
Neutrophils
Complementary DNA
Tissue
Phenotype
Defects
Proteins
In Vitro Techniques
IgA receptor

Keywords

  • Hematopoiesis
  • PU.1
  • Spi-B

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Spi-B can functionally replace PU.1 in myeloid but not lymphoid development. / Dahl, Richard; Ramirez-Bergeron, Diana L.; Rao, Sridhar; Simon, M. Celeste.

In: EMBO Journal, Vol. 21, No. 9, 01.05.2002, p. 2220-2230.

Research output: Contribution to journalArticle

Dahl, Richard ; Ramirez-Bergeron, Diana L. ; Rao, Sridhar ; Simon, M. Celeste. / Spi-B can functionally replace PU.1 in myeloid but not lymphoid development. In: EMBO Journal. 2002 ; Vol. 21, No. 9. pp. 2220-2230.
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