Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent.
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 lambda5, 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.
Ikawa
Tomokatsu
T
Division of Biological Sciences, 0377 University of California, San Diego, La Jolla, CA 92093, USA.
Kawamoto
Hiroshi
H
Wright
Lilyan Y T
LY
Murre
Cornelis
C
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins; D019070:Cell Lineage; D002478:Cells, Cultured; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D015322:Gene Rearrangement, B-Lymphocyte; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D051820:TCF Transcription Factors; D013997:Time Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C075668:Tcf3 protein, mouse; C544913:Tcf7l1 protein, mouse