Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent

Tomokatsu Ikawa, Hiroshi Kawamoto, Lilyan Y.T. Wright, Cornelis Murre

Research output: Contribution to journalArticlepeer-review

117 Citations (Scopus)

Abstract

E2A proteins are essential for the development of B cells beyond the progenitor cell stage. Here we have isolated E2A-deficient bone marrow-derived cells that have the ability to grow long-term in vitro and coexpress, at low levels, regulators of different hematopoietic cell lineages. When transferred into lethally irradiated hosts, E2A-deficient hematopoietic progenitor cells reconstitute the T, NK, myeloid, dendritic, and erythroid lineages but fail to develop into mature B lineage cells. Enforced expression of E47 in E2A-deficient hematopoietic progenitor cells directly activates the transcription of a subset of B lineage-specific genes, including λ5, mb-1, and Pax5. In contrast, E47 inhibits the expression of regulators of other hematopoietic lineages, including TCF-1 and GATA-1. These observations indicate that E2A-deficient hematopoietic progenitor cells remain pluripotent after long-term culture in vitro and that E2A proteins play a critical role in B cell commitment.

Original languageEnglish
Pages (from-to)349-360
Number of pages12
JournalImmunity
Volume20
Issue number3
DOIs
Publication statusPublished - 03-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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