TY - JOUR
T1 - Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent
AU - Ikawa, Tomokatsu
AU - Kawamoto, Hiroshi
AU - Wright, Lilyan Y.T.
AU - Murre, Cornelis
N1 - Funding Information:
We thank members of the Murre laboratory for helpful comments and suggestions. We thank Yasu Agata for providing valuable reagents, Ken Dorshkind for S17 cells, and Jim Hagman for retroviral constructs. Funding was provided by the NIH (C.M.).
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(04)00049-4
DO - 10.1016/S1074-7613(04)00049-4
M3 - Article
C2 - 15030778
AN - SCOPUS:1642311876
SN - 1074-7613
VL - 20
SP - 349
EP - 360
JO - Immunity
JF - Immunity
IS - 3
ER -
