Requirement of Transcription Factor PU.1 in the Development of Multiple Hematopoietic Lineages

TLDR

PU.1 is a hematopoietic‑specific ETS family transcription factor. The study used gene targeting to generate mice with a PU.1 locus mutation. Homozygous PU.1 mutants die late in gestation and show a universal multilineage progenitor defect that impairs B and T lymphocyte, monocyte, and granulocyte development, while megakaryocyte and erythroid progenitors are normal but erythroblast maturation can be impaired, underscoring PU.1’s essential role in multipotential progenitor development.

Abstract

The transcription factor PU.1 is a hematopoietic-specific member of the ets family. Mice carrying a mutation in the PU.1 locus were generated by gene targeting. Homozygous mutant embryos died at a late gestational stage. Mutant embryos produced normal numbers of megakaryocytes and erythroid progenitors, but some showed an impairment of erythroblast maturation. An invariant consequence of the mutation was a multilineage defect in the generation of progenitors for B and T lymphocytes, monocytes, and granulocytes. Thus, the developmental programs of lymphoid and myeloid lineages require a common genetic function likely acting at the level of a multipotential progenitor.