B-myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development

Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3122-7. doi: 10.1073/pnas.1315464111. Epub 2014 Feb 10.

Abstract

The B-myb (MYBL2) gene is a member of the MYB family of transcription factors and is involved in cell cycle regulation, DNA replication, and maintenance of genomic integrity. However, its function during adult development and hematopoiesis is unknown. We show here that conditional inactivation of B-myb in vivo results in depletion of the hematopoietic stem cell (HSC) pool, leading to profound reductions in mature lymphoid, erythroid, and myeloid cells. This defect is autonomous to the bone marrow and is first evident in stem cells, which accumulate in the S and G2/M phases. B-myb inactivation also causes defects in the myeloid progenitor compartment, consisting of depletion of common myeloid progenitors but relative sparing of granulocyte-macrophage progenitors. Microarray studies indicate that B-myb-null LSK(+) cells differentially express genes that direct myeloid lineage development and commitment, suggesting that B-myb is a key player in controlling cell fate. Collectively, these studies demonstrate that B-myb is essential for HSC and progenitor maintenance and survival during hematopoiesis.

Keywords: myelodisplastic syndrome; myeloipiesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation / physiology*
  • Crosses, Genetic
  • DNA Primers / genetics
  • Flow Cytometry
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / physiology*
  • Immunoblotting
  • Mice
  • Mice, Inbred C57BL
  • Microarray Analysis
  • Myeloid Progenitor Cells / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / metabolism*

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • Mybl2 protein, mouse
  • Trans-Activators

Associated data

  • GEO/GSE53875