Brown adipocyte progenitors in human skeletal muscle

Abstract

This invention relates to brown adipose tissue (BAT) progenitor cells and methods for isolating BAT progenitor cells from skeletal muscle. BAT progenitor cell surface markers and medium and agents for inducing cell differentiation into brown adipocytes are also provided. In some embodiments, the BAT progenitor cell expresses a first cell surface marker associated with endothelial cells, the first cell surface marker being detectable in an antibody based assay using a first antibody. In addition, the BAT progenitor cell can be substantially free of a second cell surface marker associated with endothelial cells, the second cell surface marker being substantially undetectable in said antibody based assay using a second antibody. The BAT progenitor cell can also be substantially free of additional cell surface markers.

We claim: 
     
         1 . A brown adipose tissue (BAT) progenitor cell,
 wherein the BAT progenitor cell is isolated from human skeletal muscle and capable of differentiating into brown adipocyte,   wherein the BAT progenitor cell expresses a first cell surface marker associated with endothelial cells, said first cell surface marker being detectable in an antibody based assay using a first antibody; and   wherein the BAT progenitor cell is substantially free of a second cell surface marker associated with endothelial cells, said second cell surface marker being substantially undetectable in said antibody based assay using a second antibody.   
     
     
         2 . The BAT progenitor cell of  claim 1 , further comprising at least one of:
 wherein the BAT progenitor cell is substantially free of a third cell surface marker associated with hematopoietic cells, said third cell surface marker being substantially undetectable in said antibody based assay using a third antibody;   wherein the BAT progenitor cell is substantially free of a fourth cell surface marker associated with myogenic cells, said fourth cell surface marker being substantially undetectable in said antibody based assay using a fourth antibody; and/or   wherein the BAT progenitor cell is substantially free of a fifth cell surface marker associated with pericytes, said fifth cell surface marker being substantially undetectable in said antibody based assay using a fifth antibody.   
     
     
         3 . The BAT progenitor cell of  claim 1 , wherein the first cell surface marker is CD34 and the first antibody is an anti-CD34 antibody. 
     
     
         4 . The BAT progenitor cell of  claim 1 , wherein the second cell surface marker is CD31 and the second antibody is an anti-CD31 antibody. 
     
     
         5 . The BAT progenitor cell of  claim 2 , wherein the third cell surface marker is CD45 and the third antibody is an anti-CD45 antibody. 
     
     
         6 . The BAT progenitor cell of  claim 2 , wherein the fourth cell surface marker is CD56 and the fourth antibody is an anti-CD56 antibody. 
     
     
         7 . The BAT progenitor cell of  claim 2 , wherein the fifth cell surface marker is CD146 and the fifth antibody is an anti-CD146 antibody. 
     
     
         8 . The BAT progenitor cell of  claim 1 , wherein the BAT progenitor cell proliferates in a proliferation medium. 
     
     
         9 . The BAT progenitor cell of  claim 8 , wherein the proliferation medium comprises bone morphogenic protein-7 (BMP7). 
     
     
         10 . The BAT progenitor cell of  claim 1 , wherein the BAT progenitor cell differentiates into a brown adipocyte in a differentiation medium. 
     
     
         11 . The BAT progenitor cell of  claim 10 , wherein the differentiation medium is Minimal Differentiation Medium (MDM). 
     
     
         12 . The BAT progenitor cell of  claim 10 , wherein the differentiation medium comprises a peroxisome proliferator-activated receptor gamma (PPARγ) agonist. 
     
     
         13 . A population of cells isolated from skeletal muscle, comprising at least one BAT progenitor cell of  claim 1 . 
     
     
         14 . A method for identifying an agent that induces expression or activity levels of UCP1, comprising:
 providing the BAT progenitor cell of  claim 1 ;   contacting the BAT progenitor cell with an agent; and   determining if the BAT progenitor cell exhibits an increase in UCP1 expression or activity.   
     
     
         15 . A differentiation medium comprising at least one BAT progenitor cell of  claim 1 . 
     
     
         16 . The differentiation medium of  claim 15 , wherein the differentiation medium is Minimal Differentiation Medium (MDM). 
     
     
         17 . The differentiation medium of  claim 15 , wherein the differentiation medium comprises a peroxisome proliferator-activated receptor gamma (PPARγ) agonist and/or bone morphogenic protein-7 (BMP7).