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 -