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

TY - JOUR

T1 - Ebf2 is a selective marker of brown and beige adipogenic precursor cells

AU - Wang, Wenshan

AU - Kissig, Megan

AU - Rajakumari, Sona

AU - Huang, Li

AU - Lim, Hee-Woong

AU - Won, Kyoung-Jae

AU - Seale, Patrick

PY - 2014/10/7

Y1 - 2014/10/7

N2 - 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.

AB - 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.

KW - Adipocytes/cytology

KW - Adipogenesis/genetics

KW - Adipose Tissue/cytology

KW - Adipose Tissue, Brown/cytology

KW - Adipose Tissue, White/cytology

KW - Animals

KW - Basic Helix-Loop-Helix Transcription Factors/genetics

KW - Biomarkers/metabolism

KW - Cell Lineage/genetics

KW - Cells, Cultured

KW - Embryo, Mammalian/cytology

KW - Flow Cytometry

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Developmental

KW - Green Fluorescent Proteins/genetics

KW - Immunohistochemistry

KW - Mice, 129 Strain

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Microscopy, Confocal

KW - Myogenic Regulatory Factor 5/genetics

KW - Oligonucleotide Array Sequence Analysis

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1073/pnas.1412685111

DO - 10.1073/pnas.1412685111

M3 - Journal article

C2 - 25197048

SN - 0027-8424

VL - 111

SP - 14466

EP - 14471

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 40

ER -