Ebf2 is a selective marker of brown and beige adipogenic precursor cells

Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14466-71. doi: 10.1073/pnas.1412685111. Epub 2014 Sep 2.

Abstract

Brown adipocytes and muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to platelet-derived growth factor α(+), myogenic factor 5(Cre)-lineage-marked cells. RNA-sequence analysis identified early B-cell factor 2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2(GFP) embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2 expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.

Keywords: beige adipocyte; brown adipose tissue.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipogenesis / genetics
  • Adipose Tissue / cytology
  • Adipose Tissue / embryology
  • Adipose Tissue / metabolism*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / embryology
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / embryology
  • Adipose Tissue, White / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers / metabolism
  • Cell Lineage / genetics
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Confocal
  • Myogenic Regulatory Factor 5 / genetics
  • Myogenic Regulatory Factor 5 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • Ebf2 protein, mouse
  • Myogenic Regulatory Factor 5
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE60443